Induction of spermatogenesis in men with hypogonadotropic hypogonadism.

PURPOSE: We compared our clinical experience to international standards, assessed by response to treatment and pregnancy rates to ensure our results were comparable. METHODS: Men presenting with azoospermia related to hypogonadism were recruited into a treatment programme which was managed by one person over 8 years in a secondary care facility. Treatment followed published management plans using urinary gonadotropins. Data were collected on success rates in spermatogenesis, as well as variables which might predict success, and costs. Statistical analysis used non-parametric methods. RESULTS: Of 16 men with HH, 14 achieved spermatogenesis, and 9 had sperm cryopreserved. Of those 14, 6 were successful in achieving a pregnancy with their partner from assisted conception (including ICSI) and one after natural conception. Factors identified to identify men likely to be successful in treatment were whether testicular volume was larger at onset of gonadotropins (median 10 mL) with a trend towards greater success if the cause developed after puberty. Mean treatment costs per man treated amounted to GP£4379/UD$5377 (figures for September 2020). Success rates from this treatment should exceed 70% in most clinical settings. The likelihood of success improves when testicular volume exceeded 10 mL at initiation of treatment and a trend exists whereby success is more likely whereby when hypogonadism developed after puberty. Treatment costs are at a level likely to benefit quality of life, supporting the delivery of this treatment and where necessary and possible, funding it in line with other fertility treatments. This treatment should be available much more widely as a management option for men with hypogonadism, allowing them to father a biological child, rather than using donor sperm.

Medical students and intimate examinations: What affects whether a woman will consent?

OBJECTIVE: Undergraduate medical students often struggle to gain satisfactory competence levels in intimate examination. What factors increase the likelihood of a woman allowing a student to perform an intimate examination? METHODS: Questionnaires were given to women attending a tertiary gynecology hospital. Women were asked a series of questions about what would influence their decision to agree to be examined by a student. Demographic data and data on previous gynaecological history and preferences on any student who might see them in clinic. We asked women to indicate their willingness to agree to vaginal examination (but not to undergo the examination). RESULTS: Age, parity or civil status or the source of the request did not affect willingness to have a vaginal examination. The woman's hypothetical agreement was positively affected by the student's gender (female) and age (preferring older students); positively affected by an informal/relaxed manner and smart presentation, and positively by whether the woman had experienced gynecology clinics before. An association existed between being willing to be examined and whether the student had engaged with the woman by finding out what her presenting complaint was. CONCLUSIONS: Women's willingness to agree to vaginal examination is influenced by several student-related factors, some modifiable.

Polycystic ovary syndrome (PCOS): metformin.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is classically characterised by an accumulation of incompletely developed follicles in the ovaries due to anovulation. However, since the publication of the Rotterdam criteria, there is acceptance that menstrual cycle and endocrine dysfunction with hyperandrogenism is more important in reaching the diagnosis than ultrasound findings. It is diagnosed in up to 10% of women attending gynaecology clinics, but the prevalence in the population as a whole varies from 10% to 20%, depending on which diagnostic criteria are used. PCOS has been associated with hirsutism, infertility, acne, weight gain, type 2 diabetes, cardiovascular disease (CVD), and endometrial hyperplasia. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of metformin on hirsutism and menstrual frequency in women with PCOS? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 14 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: metformin compared with placebo/no treatment, metformin compared with weight loss intervention, or metformin compared with cyproterone acetate-ethinylestradiol.

Hemizona assay and sperm penetration assay in the prediction of IVF outcome: a systematic review.

The limited predictive value of semen analysis in achieving natural conception or in IVF outcome confirms the need for sperm function tests to determine optimal management. We reviewed HZA and SPA predictive power in IVF outcome, with statistical significance of diagnostic power of the assays. HZA was readily efficient in predicting IVF outcome, while evident inconsistency among the studies analysed framed the SPA's role in male fertility evaluation. Considerable variation was noted in the diagnostic accuracy values of SPA with wide sensitivity (52-100%), specificity (0-100%), and PPV (18-100%) and NPV (0-100%) together with fluctuation and notable differentiation in methodology and cutoff values employed by each group. HZA methodology was overall consistent with minor variation in cutoff values and oocyte source, while data analysis reported strong correlation between HZA results with IVF outcome, high sensitivity (75-100%), good specificity (57-100%), and high PPV (79-100%) and NPV (68-100%). HZA correlated well with IVF outcome and demonstrated better sensitivity/specificity and positive/negative predictive power. Males with normal or slightly abnormal semen profiles could benefit by this intervention and could be evaluated prior to referral to assisted reproduction. HZA should be used in a sequential fashion with semen analysis and potentially other bioassays in an IVF setting.

Trends in procedures for infertility and caesarean sections: was NICE disinvestment guidance implemented? NICE recommendation reminders.

BACKGROUND: National Institute for Health and Clinical Excellence (NICE) clinical guidelines and subsequent NICE issued 'recommendation reminders' advocate discontinuing two fertility procedures and caesarean sections in women with hepatitis. We assess whether NICE guidance in 2004 and recommendation reminders were associated with a change in the rate of clinical procedures performed. METHODS: Routine inpatient Hospital Episode Statistics (HES) data were extracted from the HES database for 1st April 1998 to 31st March 2010 using OPCS procedure codes for varicocele operations in infertile men, endometrial biopsies in infertile women and caesarean sections in women with hepatitis B or C. We used Joinpoint regression to identify points in time when the trend in procedure rates changed markedly, to identify any influence of the release of NICE guidance. RESULTS: Between 1998-2010, planned caesarean sections in women with and without hepatitis B or C increased yearly (annual percentage change (APC) 4.9%, 95% CI 2.1% to 7.7%) in women with hepatitis, compared with women without (APC 4.0% [95% CI 2.7% to 5.3%] up to 2001, APC -0.6% [95% CI -2.8% to 1.8%] up to 2004 and 1.3% [95% CI 0.8% to 1.8%] up to 2010). In infertile women under 40 years of age, endometrial biopsies for investigation of infertility increased, APC 6.0% (95% CI 3.6% to 8.4%) up to 2003, APC 1.5% (95% CI -4.3% to 7.7%) to 2007 followed by APC 12.8% (95% CI 1.0% to 26.0%) to 2010. Varicocele procedures remained relatively static between 1998 and 2010 (APC -0.5%, 95% CI -2.3% to 1.3%). CONCLUSIONS: There was no decline in use of the three studied procedures, contrary to NICE guidance, and no change in uptake associated with the timing of NICE guidance or recommendation reminders. 'Do not do' recommendation reminders may be ineffective at improving clinical practice or achieving disinvestment.

Progesterone supplementation in women with otherwise unexplained recurrent miscarriages.

CONTEXT: Recurrent miscarriages, the loss of three or more consecutive intrauterine pregnancies before 20 weeks of gestation with the same partner, affect 1%-1.5% of the pregnant population. The inadequate secretion of progesterone in early pregnancy has been proposed as a cause of recurrent miscarriages. AIMS: The aim was to investigate the efficacy of progesterone supplementation in patients with unexplained recurrent miscarriages. SETTINGS AND DESIGN: This was a 9-year cohort study of women with otherwise unexplained recurrent miscarriages who attended a recurrent miscarriage clinic in a tertiary care university hospital. SUBJECTS AND METHODS: Women with at least three unexplained recurrent miscarriages were included in the study. They were divided into three groups according to their initial and 48-h repeat progesterone levels. For women with inadequate endogenous progesterone secretion, natural progesterone vaginal pessaries 400 mg 12-hourly were offered until 12 weeks gestation. STATISTICAL ANALYSIS: Proportions and 95% confidence intervals calculated for categorical variables and the chi-square test were used to show statistical significance. Medians and ranges were calculated for noncontinuous variables. RESULTS: Pregnancy cycles (n = 203) were analyzed to examine the miscarriage rate following progesterone supplementation. Overall live birth and miscarriage rates were 63% and 36%, respectively. When analyzed by the number of previous miscarriages there was a reduction in the miscarriage rate following progesterone supplementation in women with 4 previous miscarriages when compared with historical data. CONCLUSIONS: Progesterone supplementation may have beneficial effects in women with otherwise unexplained recurrent miscarriages.

The practical implications of a raised serum FSH and age on the risk of IVF treatment cancellation due to a poor ovarian response.

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.

The predictive value of the "Hull & Rutherford" classification for tubal damage.

OBJECTIVE: This study explores the predictive value for live birth following tubal reconstructive surgery of the "Hull & 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.

Differences in time to natural conception between women with unexplained infertility and infertile women with minor endometriosis.

BACKGROUND: Opinion remains divided as to whether finding endometriotic lesions in the absence of adhesions has an adverse effect on the likelihood of conception. METHODS: 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. RESULTS: Women with endometriosis were found to have a lower probability of pregnancy compared with women with unexplained infertility (36% versus 55%; P<0.05). 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. CONCLUSIONS: 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

Tubal damage in infertile women: prediction using chlamydia serology.

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 <1:64-1:4096) were significantly (P < 0.001) higher than in women with endometriosis alone (median <1:64; range <1:64-1:512) or those with a normal pelvis (median <1:64; range <1:64-1:1024). Women with positive titres were more likely to have pelvic adhesions than tubal occlusion unless titres were very high, when tubal damage was likely to be more severe. CONCLUSIONS: CATs are of predictive value in the detection of tubal damage and are quantitatively related to the severity of damage. For practical clinical purposes, Chlamydia serology is useful mainly as a screening test for the likelihood of tubal damage in infertile women and may facilitate decisions on which women should proceed with further investigations without delay.

Traditional finals and OSCEs in predicting consultant and self-reported clinical skills of PRHOs: a pilot study.

INTRODUCTION: As we move from standard 'long case' final examinations to new objective structured formats, we need to ensure the new is at least as good as the old. Furthermore, knowledge of which examination format best predicts medical student progression and clinical skills development would be of value. METHODS: A group of medical students sat both the standard long case examination and the new objective structured clinical examination (OSCE) to introduce this latter examination to our Medical School for final MB. At the end of their pre-registration year, the group and their supervising consultants submitted performance evaluation questionnaires. RESULTS: Thirty medical students sat both examinations and 20 returned evaluation questionnaires. Of the 72 consultants approached, 60 (83%) returned completed questionnaires. No correlation existed between self- and consultant reported performance. The traditional finals examination was inversely associated with consultant assessment. Better performing students were not rated as better doctors. The OSCE (and its components) was more consistent and showed positive associations with consultant ratings across the board. DISCUSSION: Major discrepancies exist between the 2 examination formats, in data interpretation and practical skills, which are explicitly tested in OSCEs but less so in traditional finals. Standardised marking schemes may reduce examiner variability and discretion and weaken correlations across the 2 examinations. This pilot provides empirical evidence that OSCEs assess different clinical domains than do traditional finals. Additionally, OSCEs improve prediction of clinical performance as assessed by independent consultants. CONCLUSION: Traditional finals and OSCEs correlate poorly with one another. Objective structured clinical examinations appear to correlate well with consultant assessment at the end of the pre-registration house officer year.

Medical student awareness of sexual health is poor.

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.

Pre-ovulatory granulosa cells of infertile women with endometriosis are less sensitive to luteinizing hormone.

PROBLEM: Reduced fertilization rates in women with minor endometriosis may be the result of direct effects on the ovary or to primary dysfunction within the hypothalamic-pituitary-ovarian axis. This controlled study was designed to examine the steroidogenic potential of luteinized granulosa cells in women with minor endometriosis. METHOD OF STUDY: Granulosa cells were harvested at oocyte recovery and incubated for 3 hr in increasing concentrations of luteinizing hormone (LH). The dissociation constant for added concentrations of LH was computed (as Km LH) and the results were compared between women with endometriosis and controls. RESULTS: Women with minor endometriosis had a higher dissociation constant than women with tubal damage [Km 0.98 (0.58-9.24) versus 0.33 (0.28-0.72) ng/mL, P = 0.019], indicating reduced sensitivity to LH. CONCLUSIONS: In women with endometriosis, granulosa cells were less sensitive to LH stimulation. This provides further evidence for primary ovarian dysfunction as a significant contributory cause of the associated subfertility.

Quadruplet pregnancy following transfer of two embryos: Case report.

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.

Homonymous hemianopia following a triplet pregnancy: post-natal cerebral vasculitis or atypical eclampsia.

A 46-year-old woman with a triplet pregnancy developed seizures, an oculogyric crisis and a homonymous hemianopia post-natally. Abnormal neuroimaging studies and lumbar puncture suggested possible cerebral vasculitis. Treatment with aciclovir and prednisolone resulted in a slow resolution of symptoms. This case highlights the difficulty in distinguishing eclampsia from rarer neurological causes of peripartum seizures.

Endometriosis and infertility: the debate continues.

A causal relationship between minor endometriosis and infertility or subfertility has not yet been demonstrated, although a significant association is shown by prevalence studies. This article critically reviews the evidence for pituitary-ovarian dysfunction as a cause for subfertility in women with minor endometriosis. The lack of fertile controls with endometriosis presents a methodological problem. Group comparison in studies using tubal infertility cases as controls has demonstrated impaired follicular growth, reduced circulating oestradiol concentrations during the preovulatory phase and oestradiol and progesterone during the early luteal phase, and disturbed luteinizing hormone (LH) surge patterns. LH concentration in preovulatory follicular fluid is also reduced, and granulosa cells collected at the same time have impaired steroidogenic capacity in vitro. However, these findings are not consistent in published studies. Significantly lower oocyte fertilization rates (49%) are found compared with controls (69%), even after maximum stimulation with exogenous follicle-stimulating hormone and human chorionic gonadotrophin (52% versus 69%). The implantation rate is also lower (11% versus 13%). An inherent disorder of follicular function seems likely, and LH surge impairment is probably a secondary effect. Impairment of oocyte fertilization would thus contribute substantially to the natural subfertility associated with endometriosis, but in vitro fertilization is still successful as excess numbers of oocytes are available.