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Background: Gonadotropin injections for fertility treatment regimens are usually self-injected, typically over 8 to 12 days during the assisted reproductive technology cycle. Parenteral gonadotropins are available in different formulations and administered through various systems. A user experience study and risk assessment were performed to evaluate different product types for risks to the patient when preparing and administering injections.Methods: Nine women of child-bearing age each prepared and administered injections of six products representing single-and multidose vials of menotropin for reconstitution (Merional® and Menopur®), follicle stimulating hormone (FSH) reusable pen injectors with (Puregon®) and without cartridges (Gonal-f®), and single-use FSH pre-filled pens (Bemfola®). Risk assessments based on user feedback were made with reference to EU regulations for implementing practices for safe use of injectable products. Results: Products requiring reconstitution with diluent in glass ampoules were associated with medium risk for sharps injury and a lower level of user confidence. Pen injectors were considered easy-to-use, with a low risk of sharps injury. Single-use pens were associated with the lowest risk of dosing errors.Conclusions: The study identifies differences in the risks for both sharps injuries and dosing errors between FSH delivery options that practitioners should consider when making a treatment choice.

Bemfola® is a recombinant follicle-stimulating hormone (FSH) used during infertility treatment. One main differentiator between FSH products is their delivery device; consisting of multi-dose pens (Gonal-f®), vials or multi-dose preparations (Menopur®), or adjustable daily disposable dose pens (Bemfola®). To determine the potential impact of delivery device on drug wastage during infertility treatment this study retrospectively analysed Gonal-f® and Menopur® prescription and usage data from five UK clinics. Incurred drug wastage was then compared to potential Bemfola® drug wastage. Data collected included: (i) number of treatment cycles; (ii) daily FSH dose; (iii) length of treatment; (iv) dose adjustment following ultrasound scan; (v) FSH formulation(s) prescribed and (vi) agonist/antagonist protocol used. Treatment with Gonal-f® (4078 cycles) and Menopur® (646 cycles) resulted in an average drug wastage of 160 and 294 IU per treatment cycle. Use of Bemfola® instead of Gonal-f® and Menopur® may r...

The English-language literature was reviewed to examine the evidence base for strategies that have been used to prevent ovarian hyperstimulation syndrome (OHSS). Prediction of OHSS by pretreatment patient characteristics and ovarian response parameters is unreliable, with a significant number of OHSS cases occurring in patients not thought to be high risk, while the majority of 'high-risk' cycles do not result in OHSS. Alternatives to ovarian stimulation should always be considered, depending on the clinical situation. Monofollicular ovulation induction with a cautious step-up regime carries a lower risk of overstimulation than step-down regimes. In in vitro fertilization (IVF) cycles, a low starting dose of follicle-stimulating hormone (FSH) and the use of 5000 iu human chorionic gonadotrophin (hCG) for final follicular maturation may benefit patients at high risk of OHSS. The role of GnRH antagonists is unclear. In women with polycystic ovaries, who are undergoing ovarian stimulation for IVF, metformin co-treatment may reduce the risk of OHSS. Coasting of cycles with over-response is associated with a reduced risk of OHSS, although precise criteria for initiating and ending coasting are not definable at present. Elective cryopreservation of all embryos prevents late OHSS, but its value has been poorly researched. The literature does not support a role for intravenous albumin, administered around the time of oocyte retrieval, in preventing OHSS. Evidence is insufficient regarding a possible role for hexa-ethyl starch. hCG should not be used for luteal support, as it is associated with a higher risk of OHSS, and equivalent pregnancy rates are obtained with the use of progesterone.

Objective This study explores the predictive value for live birth following tubal reconstructive surgery of the ‘Hull and Rutherford’ (H&R) classification system. Design Retrospective cohort study. Setting Tertiary infertility referral service, University of Bristol. Population Infertile women younger than 40 years with tubal damage undergoing tubal surgery. Methods Women (n= 192) were grouped according to three severity grades of disease based on the H&R classification. Essentially, the main features of grade I tubal damage were filmy adhesions, whereas grades II and III referred to unilateral severe damage and bilateral severe damage, respectively. Standard surgical techniques were employed. Pregnancy and live birth rates were calculated and compared using time-specific univariate Kaplan–Maier curves and multivariate Cox's regression analysis. Main outcome measures Pregnancy, ectopic and live birth within three years of surgery. Results A significant trend towards higher ectopic pregnancy rates (P < 0.001) with increasing severity of tubal damage was noted, but not miscarriage rates. Univariate analysis revealed significant differences in the live birth rates of 69%, 48% and 9% for grades I, II and III, respectively. Multivariate analysis (controlling for age, duration of and primary infertility) confirmed these differences to be significant with risk ratios of 13.7 (95% CI: 4.49–41.9) and 6.54 (95% CI: 2.48–17.24) for grades I and II disease, respectively, compared with grade III disease, used as the reference. Conclusions The H&R classification is a simple classification system that is able to distinguish women into three distinct groups giving a favourable, fair and poor prognosis for live birth following tubal surgery.

BACKGROUND: Traditional campus-based models of education are unsuitable to many, particularly if in full-time employment supporting families, whereas the Internet now permits new models of education. Following an iterative process of development and evaluation in 2001, the University of Bristol launched a masters programme covering reproduction and development delivered principally over the Internet. METHODS: Students attend short biannual residential workshops and the rest of the course is delivered online. In 2003, the 20 active students were invited to complete a structured online questionnaire. RESULTS: The 18 students completing the questionnaire identified distance learning as the key factor in their course selection. Most students felt that residential workshops aided subsequent electronic communication. Discussion of ideas is an essential component of postgraduate courses and web-based discussion forums appeared to provide an acceptable medium for this. The use of web-based audio lectures and computer-assisted assessments was well received. Also these systems may reduce disadvantages overseas students encounter when completing assessments in their non-native language. CONCLUSIONS: The overall positive response from students (and their tutors) to using the Internet for multiprofessional reproductive medicine education is encouraging and has wider potential in the future.

Opinion remains divided as to whether finding endometriotic lesions in the absence of adhesions has an adverse effect on the likelihood of conception.This was a retrospective study of 192 fully investigated infertile couples, followed up for up to 3 years following laparoscopy. Women studied were ovulating,40 old years and their partners had normal sperm parameters. All 117 women with unexplained infertility and 75 with minimal/mild endometriosis without adhesive disease were managed conservatively.Women with endometriosis were found to have a lower probability of pregnancy compared with women with unexplained infertility (36% versus 55%; P0.05). Other factors adversely associated with pregnancy were primary infertility, smoking and longer duration (3 years) of infertility. However, the effects of duration of infertility and primary infertility were not observed to be statistically significant for women with endometriosis.The findings, although undertaken in a select population undergoing laparoscopy, suggest the likelihood of pregnancy is reduced in infertile women with minimal/mild endometriosis compared with those infertile women with a normal pelvis. Duration of infertility and a previous history of pregnancy are important in predicting the likelihood of pregnancy in women with no obvious cause for their infertility (unexplained), whilst the relationship may be more complex in women with minor endometriosis

BACKGROUND: The study explores the relationship between serum chlamydia antibody titres (CATs) and detection of tubal damage in infertile women. METHODS: The tubal status and pelvic findings in 1006 women undergoing laparoscopy for infertility were related to CAT, which was measured using the whole-cell inclusion immunofluorescence test. RESULTS: A negative correlation between CAT and age was noted. A linear trend between serum CAT and the likelihood of tubal damage, including severe damage, was observed (P < 0.001). Titres in women with tubal damage (median 1:1024; range

The aim of the study was to assess sexual health knowledge of medical students. Participants from the student population of an English Medical School (University of Bristol) were asked to fill in a questionnaire on the Internet about sexual health issues. The number of correct responses to each question was analysed according to participants' gender and medical school year. While certain issues relating to sexually transmitted infections, contraception and confidentiality in HIV testing were well understood, there was poor knowledge about the failure rate of condoms, abortion rates and prevalence of chlamydia. Women knew more about the contraceptive pill than men. Although increased years of medical training had some benefit in improving the accuracy of knowledge, this effect was surprisingly small. Most medical students have inaccurate factual knowledge about certain important sexual health issues. We consider this to reflect poorly on sexual health awareness in young people in general. There is need for greater sexual health education for future doctors and for the general public.

BACKGROUND: Conception following gonadotrophin-stimulated IVF and embryo transfer has been associated with a higher intrafollicular cortisol:cortisone ratio and decreased metabolism of cortisol to cortisone. The role of glucocorticoids in human oocyte maturation is not fully understood, but active glucocorticoid (cortisol) may be important. This study relates intrafollicular cortisol and cortisone concentrations to oocyte fertilization and embryo implantation in unstimulated cycles. METHODS: Patients aged

Background The present study addresses the issue of biological ageing of the oocyte (as indicated by basal serum FSH levels) versus chronological ageing. Methods 1019 infertile but ovulating women were studied in their first cycle of IVF treatment. A series of logistic regression models were developed to assess statistical significance of effects of age and FSH on implantation rates and live babies born. Results The number of oocytes retrieved and embryos available for transfer declined with increasing age and basal serum FSH concentrations. Fertilizing ability of oocytes increased with advancing age but was not affected by FSH concentrations. Although the number of oocytes or embryos available for transfer had no independent effect on implantation rates, the implanting ability of fertilized oocytes (embryos) was inversely related to increasing age and independently to FSH. The chance of a baby being born, however, was determined more by age than by serum FSH. Conclusions Ovarian ageing affecting oocyte quality and fecundity can occur independently of chronological age. This has important practical implications whereby serum basal FSH measurement may be a valuable prognostic index, though chronological age remains important.

Ovarian hyperstimulation syndrome (OHSS) most commonly follows human chorionic gonadotrophin (hCG) administration as part of supraphysiological ovarian stimulation in assisted conception cycles. If risk factors for OHSS are detected pretreatment, stimulation regimes should be modified. Monitoring of ovarian response during gonadotrophin stimulation may identify high-risk cycles, allowing further gonadotrophin to be withheld till the ovarian response settles to safe levels. Complete avoidance of hCG prevents OHSS, but may not be acceptable to patients. Luteal hCG exposure can be minimized by freezing all embryos or by using luteal support with progesterone in preference to hCG. Patients with moderate/severe OHSS should be admitted and receive sympathetic counselling, thrombosis prophylaxis and symptomatic treatment for pain and nausea. Oral rehydration should be encouraged, with intravenous crystalloids for cases with significant nausea. Volume expanders should be used for resistant dehydration and oliguria. Paracentesis may help patients with tense ascites. Complications may require multidisciplinary care.

BACKGROUND: Cancellation of assisted conception cycles because of poor ovarian response to gonadotrophins is a significant problem in assisted reproduction. Various adjuvant treatments have been suggested to improve responsiveness. This study reports on the potential benefits of low dose dexamethasone. METHODS: Patients

Ovarian hyperstimulation syndrome remains a significant but incompletely understood complication of ovarian stimulation. Evidence has accumulated regarding a role for various cytokines, in particular vascular endothelial growth factor, in its occurrence. However, the pathogenesis of ovarian hyperstimulation syndrome is likely to be complex and may involve a network of interacting cytokines and endocrine factors. Recent studies suggest links between specific cytokines and specific functional abnormalities in severe ovarian hyperstimulation syndrome. Two clinical forms of ovarian hyperstimulation syndrome may be distinguished, based on time of onset, with implications for the prediction and prevention of ovarian hyperstimulation syndrome in clinical practice.

Objective To determine the Information Technology (IT) infrastructure available to, and IT skills of, obstetric specialiast registrars across the South West Denery. Design Open prospective study. Setting NHS Hospitals in the South West Deanery. Methods two separate surveys. Firstly, the computer equipment available to trainees was determined at each hospital in the deanery on site using a software programme. Secondly, IT skills of a sample of 22 specialist registrars were assessed using a checklist at a series of four workshops. Main outcome measures Computers with sufficient specification to use CD-ROMs, to access the Inter- net, and to support data-, audio- and video-conferencing. The number of trainees with IT skills to use a computer-aided learning package and the Internet. Results Sixty-six percent of trainees have access to a computer with a CD-ROM drive. Sixty-six percent also have access to the Internet at their place of work. Thirteen percent have access to data-conferencing but there were no computers in the Deanery able to support audio- or video-conferencing. lbenty-five percent of trainees have no IT skills and require basic training in the use of computers. Thirty-six percent of our sample would require training to be able to use computer-based tutorials programs. Seventy- seven percent of trainees require training to be able to use the Internet without assistance. Conclusion A significant minority of trainees do not have access to computers with sufficient specification to run basic tutorial programmes or access the Internet. Similarly, a large minority of trainees do not even have a basic knowledge of computer technology and IT training is required for the majority of trainees for them to reap the potential benefits which computer-based tutorials systems and the Internet can give.

This review briefly assesses what a practitioner should do when a couple has problems conceiving. Around one in four couples present to their GP to discuss infertility, and the majority of them will ultimately have a child. It is therefore appropriate to take a positive approach, and to see this first consultation as an opportunity to discuss pre-pregnancy care. This maximises the couple's chances of having a healthy baby and provides an opportunity to assess factors which might affect their fertility. The review offers a number of brief questions and answers on how to assess ovulation indicators and referral, basic infertility treatments, assisted reproduction technologies and the relevance of the NICE national guidelines on managing infertility treatment.

This review examines recent evidence suggesting a role for the immune system, in particular cytokines, in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). Ovarian tissue is known to contain cells capable of producing a range of immunological mediators and the concentrations of these have been shown to be elevated in serum and ascitic fluid from women with established OHSS. Available evidence points to a role for vascular endothelial growth factor and interleukin-2, possibly acting through other intermediary cytokines, in the pathogenesis of OHSS. However, each individual has a unique cytokine profile and several cytokines may share biological actions, making it difficult to interpret data on isolated cytokine concentrations from relatively small numbers of patients. Improved understanding of the role of the immune system in the development of OHSS may have implications for the prediction, prevention and management of this iatrogenic condition.

We questioned the policy of routine microbiological culture of semen prior to in-vitro fertilization (IVF) with a view to prescribing antibiotics to reduce the risk of introducing seminal infection into the embryo culture system. An initial retrospective study examined serum microbiology reports of 449 couples undergoing IVF or gamete intra-Fallopian transfer (GIFT). In semen samples taking/=1 days to reach the microbiology laboratory compared with same-day delivery there was increased frequency of significant culture of enterococci (27 versus 15%, P0.01). In samples taking/=2 days there was increased frequency of significant culture of Gram-negative bacilli (31 versus 12%, P0.01) and of overall culture of other potentially pathogenic organisms (26 versus 14%, P0.01). We questioned diagnostic accuracy and relevance. Therefore, in a prospective study, semen and high vaginal swabs obtained on the day of oocyte collection were cultured from 100 couples having IVF or GIFT, of whom 52 male partners had been treated with antibiotics following positive pre-IVF semen culture. The presence of bacteria in semen samples used only for IVF (n = 90) did not reduce fertilization rates nor lead to infection of the embryo culture system. However, there was an increased incidence of significant culture of vaginal Gram-negative bacilli in patients with treated partners compared with untreated partners [15/52 (29%) versus 5/48 (10%), P0.05]. Thus antibiotic therapy in the male partner may increase the likelihood of inoculation of antibiotic-resistant pathogenic bacteria from the vagina into the embryo culture system during vaginal oocyte collection. In asymptomatic patients, microbiological screening of semen samples prior to IVF treatment and subsequent treatment with antibiotic therapy in those with positive cultures appears to be unnecessary and may be detrimental to IVF outcome.

Following a long period of secondary unexplained infertility, a couple had assisted conception treatment with IVF and transfer of two embryos 2 days later. The woman conceived and was found to have a quadruplet pregnancy. Following spontaneous labour onset at 34 weeks gestation, she was delivered by immediate Caesarean section. All four babies (three boys, one girl) were eventually discharged home with the mother. All the boys were found to be of differing zygosity. The quadruplet pregnancy was attributed to natural conception following intercourse and fertilization of oocytes not collected at the time of IVF. The wisdom of intercourse during a cycle of IVF is discussed.

Following a detailed information technology survey in the South West Deanery, an Internet educational programme in reproductive medicine was constructed, delivered and assessed. The course followed a problem-based approach using case studies, using an education website and electronic mail (e-mail) to communicate between trainees and trainers. Independent evaluation revealed a high level of satisfaction for both trainees and trainers with an increase in trainees' confidence to deal with patients following the course. This study suggests that the Internet may be used effectively to deliver postgraduate medical education, if the training programme is designed appropriately to computer infrastructure and the computer literacy of the users.

The objective of this study was to investigate whether a change in assisted hatching (AH) technique from total to partial penetration of the zona pellucida improved the outcome of IVF and intracytoplasmic sperm injection cycles where AH was indicated. This was an observational study conducted from the beginning of January 2000 to the end of April 2005. Total AH was performed in 312 cycles, while partial AH was performed in 592 cycles. In women of all ages, implantation, clinical pregnancy and live birth rates were higher in the partial AH group than in the total AH group (12.6 versus 7.2%, P = 0.0001; 22.3 versus 15.7%, P = 0.02; 18.2 versus 12.5%, P = 0.03 respectively). The benefit of partial AH was most marked in women under 38 years old (i.e. the recurrent implantation failure group). The authors conclude that partial AH is associated with higher implantation and pregnancy rates than total AH, especially in women under 38 years old who suffer from recurrent implantation failure.

Some evidence suggests that complementary and alternative medicine (CAM) has found increased utilisation among patients seeking infertility treatment, although there is little information available to quantify this phenomenon. This is important information as there is marketing for CAM directed to this group and professionals need to be aware of the treatments their patients are receiving. Patients attending for infertility diagnosis and treatment often ask the physician about CAM; this paper seeks to compare the prevalence of CAM use among infertility patients in National Health Service (NHS) and private clinics. This paper provides results of a survey of couples (n = 400) divided equally between NHS and private settings. Our data suggest a high use of CAM particularly among female private patients, although patients appear sceptical of the efficacy of such treatment which is consistent with the literature.

This study explores the predictive value for live birth following tubal reconstructive surgery of the "HullRutherford" (HR) classification system.Retrospective cohort study.Tertiary infertility referral service, University of Bristol.Infertile women younger than 40 years with tubal damage undergoing tubal surgery.Women (n= 192) were grouped according to three severity grades of disease based on the HR classification. Essentially, the main features of grade I tubal damage were filmy adhesions, whereas grades II and III referred to unilateral severe damage and bilateral severe damage, respectively. Standard surgical techniques were employed. Pregnancy and live birth rates were calculated and compared using time-specific univariate Kaplan-Maier curves and multivariate Cox's regression analysis.Pregnancy, ectopic and live birth within three years of surgery.A significant trend towards higher ectopic pregnancy rates (P0.001) with increasing severity of tubal damage was noted, but not miscarriage rates. Univariate analysis revealed significant differences in the live birth rates of 69%, 48% and 9% for grades I, II and III, respectively. Multivariate analysis (controlling for age, duration of and primary infertility) confirmed these differences to be significant with risk ratios of 13.7 (95% CI: 4.49-41.9) and 6.54 (95% CI: 2.48-17.24) for grades I and II disease, respectively, compared with grade III disease, used as the reference.The HR classification is a simple classification system that is able to distinguish women into three distinct groups giving a favourable, fair and poor prognosis for live birth following tubal surgery.

Purpose: Chronological age, or biological age as indicated by elevated FSH levels, are related to ovarian reserve. This study addresses the likelihood of cancellation of IVF treatment due to a poor ovarian response utilising both basal serum FSH and woman's age. Methods: A prospective cohort of 536 infertile but ovulating women were studied in their first cycle of IVF treatment. Standardised methods of pituitary desensitisation and ovarian stimulation prior to IVF treatment were employed. Treatment cycles cancelled due to a poor ovarian response to gonadotrophins were studied. A series of logistic regression models were used to explore the probabilities of cancellation in relation to age and FSH. Results: Both age and basal serum FSH levels were independently associated with the risk of treatment cancellation. A low risk of treatment cancellation was observed in women under the age of 35 irrespective of serum FSH, however in older women the risk of treatment cancellation was most likely in women with a high FSH. Conclusions: In combination both age and FSH may serve as a valuable indicator of poor ovarian response leading to treatment cancellation. However, among older women FSH has particular importance, while less so in younger women with regular menstrual cycles.

Whereas modern assisted conception with such techniques as in vitro fertilisation now helps many subfertile couples to fulfil their ambition to have a child, it has not been without a price. The increased incidence of multiple pregnancies, with their attendant maternal and perinatal sequelae following assisted conception is well known, but perinatologists may be less familiar with the Ovarian Hyperstimulation Syndrome (OHSS) which is the other major complication when controlled ovarian hyperstimulation is used during assisted conception treatment. Mild forms of OHSS are common and require no more than symptomatic treatment. Severe forms of OHSS are uncommon occurring in 0.6% to 14% of IVF cycles [15, 5], but are nonetheless very important to identify as they may lead to thrombo-embolic disease, cardiorespiratory dysfunction, renal failure and even death [6]. This review considers whether OHSS may be related to multiple pregnancy by reviewing the available literature and local experience.

BACKGROUND: Insulin-like growth factor-1 (IGF-1) is known to play a role in ovarian follicular development augmenting the action of FSH. Low intrafollicular concentrations have been detected in women who respond poorly togonadotrophins. This study addresses the relationship between serum IGF-1 levels following pituitary desensitization and ovarian response to gonadotrophin stimulation. METHODS: This is a case-control study of 78 patients undergoing IVF-embryo transfer treatment. Thirty-nine strictly-defined poor responder patients requiring 50 or more ampoules (75 IU FSH) to reach oocyte retrieval were compared with 39 age-matched normal responders, requiring fewer than 50 ampoules. IGF-1 concentrations were determined by extraction radioimmunoassay on serum samples obtained after pituitary desensitization but prior to gonadotrophin stimulation. RESULTS: Despite highly significant differences in measures of ovarian response between groups, the mean serum IGF-1 concentration was not statistically significantly different between poor and normal responders {(31.5 nmol/l [95% confidence interval (CI) 28.5-34.5] versus 34.5 nmol/l (95% CI 31.8-37.2)} respectively. No correlation between oocyte number or total gonadotrophin used and serum IGF-1 concentration was observed. CONCLUSION: Whilst IGF-1 influences ovarian follicular development this study suggests that serum IGF-1 does not predict ovarian response and does not differentiate between critically-defined poor and normal responders.

A pilot course was carried out aiming to evaluate the relative potential of email and World Wide Web-based discussion boards to deliver an online course in reproductive medicine to 18 doctors training in obstetrics and gynecology, distributed around the South West region of England. The course organisers presented one case study per month and asked participants to comment on it by electronic means. The course was evaluated for its ability to deliver and ease of access. Tutors’ and participants’ views were sought. The information gathered was incorporated into the development of further Internet-based educational projects.

Objective To determine whether serum vascular endothelial growth factor (VEGF) levels can distinguish highly responsive women who subsequently develop ovarian hyperstimulation syndrome (OHSS) from women with a similar ovarian response who do not. Design Prospective controlled study. Setting University IVF unit. Patient(s) Women undergoing IVF who met predetermined risk criteria for OHSS. Patients developing OHSS were compared with patients who did not develop OHSS. Intervention(s) Long-protocol pituitary down-regulation followed by FSH stimulation by a standard protocol without coasting. A maximum of three embryos was transferred. Vaginal progesterone was used for luteal support. Main outcome measure(s) Occurrence of OHSS; serum VEGF concentrations on the day of embryo transfer (ET) and at 5 and 10 days after ET. Result(s) Serum VEGF levels at any time point did not differ significantly between 9 OHSS cases and 9 controls. Vascular endothelial growth factor levels in samples collected from cases before the onset of OHSS were higher than levels in time-matched samples from controls (medians, 177.6 [range, 64.02–549.1] pg/mL vs. 100.7 [range, 37.59–246] pg/mL, respectively), but the difference failed to reach statistical significance ( P =.0518), and there was considerable overlap between cases and controls. Conclusion(s) Serum VEGF levels in the luteal phase do not distinguish between high-risk women who subsequently develop OHSS and women with a similar risk profile who do not develop OHSS.

In 1991, the British Fertility Society commissioned an audit subcommittee to produce an all-encompassing classification system for infertility, which could be used as the basis for national audit. Accurate diagnosis is a basic necessity of good medical practice and determines the selection of appropriate treatment. In addition, assessment of treatment outcome by audit must be related not only to the specific type and severity of the disorder, but also to a number of important compounding variables, such as age of the female partner. Severity is a key factor in the selection of the most appropriate treatment in disorders such as tubal disease and endometriosis; therefore, the classification of these conditions needs to be therapy-oriented, providing a guide to prognosis. The classification system was determined by reference to the best available published data on outcome, in terms of time-specific cumulative pregnancy rates, at the time of preparation, and on information gleaned from surveys of opinion from the members of the British Fertility Society and the British Andrology Society. When used in conjunction with an appropriate computerheld database, codification of data using a classification system provides a powerful tool for clinical audit and research. Such systems allow analysis of the relative effectiveness of different methods of treatment for various patient groups, providing meaningful comparisons among practitioners and hospitals (Jenkins, 1999). A survey published in 2000 of all in vitro fertilization (IVF) centres in the UK indicated overwhelming support for central collection of computerized data by the Human Fertilisation and Embryology Authority (HFEA), which could be extended beyond the limited current dataset if a suitable classification system was available (Keay et al., 2000). This article presents an appendix outlining the classification system as it was first proposed in 1995, so that it may act as a foundation for the future development of an updated classification that could be adopted by the profession.

ReproMED comprises a range of projects applying and researching the role of information technology to support clinical care, education and research in reproductive medicine. This article traces the development of ReproMED on the Internet and concludes by speculating on the future. The project started with a critical evaluation of the infertility information needs of general practitioners and the role of hypertext in meeting those needs, leading to the production of a ReproMED CD-Rom. However, as the project was under development in 1995, Microsoft launched its first web browser amid major expansions of the Internet, thus the project switched to a series of websites and played host to national bodies including the British Fertility Society and the British Andrology Society. After a critical evaluation of the role of the Internet in supporting postgraduate medical education in the southwest region, reproductive medicine training over the Internet was piloted. This pilot was followed by a series of similar training programmes for junior doctors, specialists and general practitioners, leading to the establishment of a formal MSc delivered principally over the Internet. In addition to professional education and research, the ReproMED websites provide patients with extensive interactive information. The future holds many exciting possibilities with rapid technological developments and ever-increasing information needs.

The prevalence of chlamydial DNA determined by PCR and in-situ hybridisation (ISH) in fresh tissue specimens (endometrium, fallopian tube and ovary) was investigated in 33 women presenting with ectopic pregnancy (EP), 14 women with tubal factor infertility (TFI) and 50 control patients from the UK and the West Indies. In the UK EP group, chlamydial DNA was detected by PCR in 56% of patients; similar results were found in the Trinidad EP group (67%). In the TFI group, chlamydial DNA was detected in (71%) of patients by PCR. The detection of Chlamydia trachomatis DNA by ISH was highest in the TFI group (43%). Women presenting with EP and TFI showed evidence of previous or current genital C. trachomatis infection, underlining the importance of this micro-organism in the development of these conditions. Importantly, chlamydial DNA could be detected in DNA preparations from the endometrium, fallopian tube and ovary of EP and TFI patients at the time of surgery.

Objective: To compare patient and cycle characteristics among three study groups: early ovarian hyperstimulation syndrome (OHSS), late OHSS, and non-OHSS. Design: Prospective observational study. Setting: University assisted conception service. Patient(s): Women undergoing in vitro fertilization, intracytoplasmic sperm injection or gamete intrafallopian transfer treatment at Bristol University In Vitro Fertilization Service between January 1, 1995, and December 31, 1998. Intervention: None. Main Outcome Measure(s): Patient age, prevalence of polycystic ovaries, gonadotropin requirement, peak serum estradiol (E 2 ) concentration, number of oocytes retrieved, clinical pregnancy rate, number of gestation sacs, and severity of OHSS. Result(s): Women with early OHSS had significantly higher serum E 2 levels and lower gonadotropin requirements than did the other groups. Cycles with either early or late OHSS had significantly more oocytes collected than those without OHSS. Serum E 2 and oocyte numbers did not accurately predict the risk of developing late OHSS. Clinical pregnancies occurred in all cycles with late OHSS, and multiple pregnancies were significantly more frequent in the late OHSS group than in the other groups. Late OHSS was more likely than early OHSS to be severe. Conclusion(s): Early OHSS relates to "excessive" preovulatory response to stimulation, whereas late OHSS depends on the occurrence of pregnancy, is likelier to be severe, and is only poorly related to preovulatory events.

Objective: To further elucidate cortisol metabolism in the follicular microenvironment at the time of oocyte retrieval, the presence of 11β-hydroxysteroid dehydrogenase (HSD) messenger (m)RNA transcripts in oocytes; cumulus cells; granulosa cells; and CD45 + , CD15 + leukocytes was assessed semiquantitatively. Design: Controlled study using semiquantitative assessment of 11β-HSD mRNA. Setting: University IVF center. Patient(s): Twenty-six patients undergoing controlled ovarian hyperstimulation for assisted conception. Intervention(s): Metaphase II oocytes; cumulus cells; granulosa cells, and CD45 + , CD15 + leukocytes from individual follicular fluid aspirates. Main Outcome Measures: Semiquantitative analysis of PCR products after total RNA extraction and complementary DNA synthesis. Result(s): Periovulatory human oocytes; cumulus cells; CD45 + , CD15 + leukocytes; and granulosa cells consistently express type 1 but not type 2 11β-HSD mRNA. Expression of mRNA is greatest in cumulus cells. Type 1 11β-HSD mRNA expression varies considerably in all cell types and among individual follicles and patients. Conclusion(s): These studies of mRNA expression suggest that the enzymes present both in and around the periovulatory oocyte will favor a high-cortisol environment.

Objective: To determine whether a relation exists between previous exposure to Chlamydia trachomatis and impaired ovarian response to gonadotropin stimulation. Design: Controlled clinical study. Setting: Two university IVF centers. Patient(s): Two hundred forty-two patients receiving IVF treatment and 81 control patients. Ninety-four patients with a poor response to IVF, defined by cycle cancellation in response to a daily stimulation dose of 300 IU of FSH, and 148 patients with a good response were matched for age. Twenty-eight pregnant controls and 53 controls of proven fertility also were included. Intervention(s): Serum samples were obtained from patients and controls. Serum levels of immunoglobulin (Ig) G antibodies to C. trachomatis were determined by ELISA. Main Outcome Measure(s): The prevalence of serum IgG antibodies to C. trachomatis in critically defined poor responders was compared with that of age-matched good responders. Result(s): A significantly higher proportion of poor responders had serum IgG antibodies to C. trachomatis compared with good responders (44.7% and 30.4%, respectively). Patients undergoing IVF had a significantly higher prevalence of IgG antibodies to C. trachomatis (36%) than did either pregnant or nonpregnant controls (12%). Conclusion(s): A significantly higher prevalence of serum IgG antibodies to C. trachomatis was observed in critically defined poor responders, suggesting a possible detrimental effect of C. trachomatis on subsequent ovarian function.

Objective: To determine the changes in follicular fluid (FF) total and free Cortisol during the LH surge in naturally ovulating women. Patient(s): Twenty-six women having diagnostic laparoscopy during the follicular phase of normal menstrual cycles were selected. Intervention(s): Blood samples were collected 1 day before, the day of, and 1 day after surgery and the results of serum E2 and LH were used to divide the cycles retrospectively into pre- and post-LH surge groups. Follicular fluid was collected during laparoscopy. Main Outcome Measure(s): Serum P, total and free Cortisol, and FF volume, E 2 , P, total Cortisol, and free Cortisol were measured on the day of surgery. Result(s): Median serum and FF P levels were significantly higher in the post-LH surge group compared with the pre-LH surge group (0.54 versus 1.54 ng/mL [1.7 versus 4.85 nmol/ L] and 5.03 versus 28.0 μ g/mL [15.8 versus 88.0 μ mol/L], respectively). Follicular fluid volume also increased significantly after the surge (2.5 versus 4.5 mL). Median serum total and free and percent free Cortisol were higher after the surge, although not significantly. In contrast, FF total, free, and percent free levels increased dramatically between pre- and post-LH surge samples (4.41 versus 43.6 ng/mL [16.0 versus 158 nmol/L], 0.138 versus 6.68 ng/mL [0.5 versus 24.2 nmol/L], and 3.3% versus 15.0%, respectively; P Conclusion(s): An increase in total and free Cortisol occurs in the follicle during the LH surge. Cortisol and its regulation by 11 β -hydroxysteroid dehydrogenase therefore may exert a physiologic role in oocyte maturation or ovulation.

It is well-known that many urinary-derived human chorionic gonadotropin (hCG) preparations contain a variety of contaminating agents that may influence the efficacy and possible safety of their application. Herein, we report the finding of epidermal growth factor (EGF) contamination and high hCG beta core levels in two leading brands of hCG - findings that will promote the use of recombinant hCG instead of the cruder, urinary-derived formulations.

Item does not contain fulltext The European Classification of Infertility Taskforce (ECIT) has been formed by ESHRE to develop a set of infertility-related codes (descriptions, interventions and outcomes) appropriate for computerization (http://www.ecit.info). In this article, ECIT reflects on previous suggestions in this Debate series, agreeing with the weaknesses of the current terminology used in reproductive medicine. Although ECIT is enthusiastic about the extension of terminology, caution is raised in abandoning familiar terms that may lead to greater rather than less confusion. Instead, ECIT suggests a way forward using structured computerized statements to retain current terms but extend their meaning.

To determine whether an inter-relationship exists between endocervical mucus pH, serum androgen levels, and waist to hip (W:H) ratio.Donor insemination clinic, University of Sheffield, Jessop Hospital, Sheffield, United Kingdom.One hundred patients receiving donor insemination.Waist, hip, height, and weight measurements were recorded for 100 patients receiving donor insemination. At the onset of the LH surge when patients attended for their first insemination, a sample of endocervical mucus and blood was taken. The Insler score of the mucus was recorded and the pH was measured with multirange pH paper. Of the 100 patients studied, 10 cases had an endocervical mucus pH6 despite Insler scores of10. Serum T, DHEAS, and androstenedione levels were measured in the 10 patients with pH6 and in 26 patients selected at random from the 90 patients with pHor = 6.The W:H ratio was significantly higher in the patients with pH6 than pHor = 6. No significant difference was seen in body mass index between the latter groups. All serum androgen levels were significantly higher in the patients with pH6 than pHor = 7.A potential link (serum androgen levels) between a powerful predictive factor of fertility (W:H ratio) and a potential mechanism of subfertility (low endocervical mucus pH) has been demonstrated. This observation warrants further detailed evaluation particularly as it has been shown that a low endocervical mucus pH may be corrected by simple inexpensive treatment.

Reviewing 780 in-vitro fertilization (IVF) cycles, where buserelin was commenced in the preceding luteal phase and human menopausal gonadotrophin on day 4 of the ensuing menses, 53 cycles were identified with sonolucent cysts (30-50 mm diameter). Of the latter 53 cycles, the serum oestradiol was significantly greater on day 4 in 22 cycles abandoned for poor follicular development than in 31 cycles which proceeded to oocyte retrieval (P less than 0.05). Of the 31 cycles proceeding to oocyte retrieval, nine had a day 4 serum oestradiol greater than 200 pmol/l (95th centile for day 4 oestradiol in patients without apparent cysts), and these cycles produced significantly fewer grade 1 embryos than the cycles with day 4 oestradiol levels less than or equal to 200 pmol/l (P less than 0.05). Six of the 53 cycles with cysts resulted in conception, and all of these cycles had a day 4 serum oestradiol less than 200 pmol/l. Among the 53 cycles with ovarian cysts, the serum progesterone on the day of abandonment in four cycles and on the day of human chorionic gonadotrophin administration in one non-abandoned cycle, was above the range established for 104 cycles without cysts. No significant difference was seen in day 4 serum androstenedione levels, and the day 4 serum progesterone was less than 5 nmol/l in all but one patient. Functional activity of ovarian cysts is associated with an adverse influence on IVF cycles.

The circulating levels of placental protein 14 (PP14) and progesterone were measured in three pregnancies resulting from the transfer of cryopreserved embryos. Two of these women had suppressed ovarian activity as a result of pituitary down-regulation with the luteinizing hormone-releasing hormone agonist (buserelin) prior to treatment with exogenous oestradiol and progesterone. After 14 days of oral oestradiol treatment and if the endometrial thickness was greater than 7 mm, progesterone was given intramuscularly for a further 14 days with embryo transfer on the third day of this treatment. On confirmation of pregnancy by human chorionic gonadotrophin analysis, progesterone administration was altered to transvaginal pessaries for maintenance of adequate progesterone levels and endometrial support. In the two women with ovarian suppression, PP14 levels remained below the 2.5th centile of the normal range for pregnancy. In the third pregnancy, embryo transfer was performed 3 days after a spontaneous luteinizing hormone surge in a normal menstrual cycle. In this pregnancy, PP14 levels were within the normal range. Ultrasonic examination confirmed three normal ongoing singleton pregnancies. These results suggest that the majority of PP14 production in normal pregnancy is under ovarian or anterior pituitary control and that the influence of progesterone is of a secondary nature.