Survey of psychological health in women with infertility.

The aims of this study were to assess mental well-being in women undergoing investigation and initial management of infertility and to determine any specific factors, such as the duration or type of infertility, that might be associated with an increased risk of psychological morbidity. A postal survey was sent to 1080 women with infertility attending gynecology outpatient departments in 12 Scottish centres. The survey included the Twelve-Item General Health Questionnaire (GHQ-12) and three multi-item scales from the Short Form Health Survey Questionnaire (SF-36). The response rate was 47.4% (512/1080) of which 507 completed the GHQ-12. Of the 507 GHQ-12 responders, 32.5% had a GHQ-12 score of > or = 8/12 suggesting they were at risk of clinically significant psychological disturbance. There were no significant associations between GHQ-12 scores and duration of infertility, the presence of existing children, or the cause of infertility. GHQ-12 scores significantly increased with the number of clinic attendances and decreased as the patient's age increased. Responders scored significantly lower on all aspects of the selected SF-36 questions as compared to published population data, suggesting poorer mental health. These standardized psychological instruments suggest that approximately 32% of women in the early stages of infertility management may be at risk of developing clinically relevant mental health problems. Psychological aspects of infertility should be addressed as part of a more holistic approach to management of these patients.

Magnetic resonance imaging of the human cervix: a study of the effects of prostaglandins in the first trimester.

BACKGROUND: To establish that magnetic resonance imaging (MRI) can provide an objective measurement of the biophysical state of the cervix and to measure the response of the cervix to prostaglandins in the first trimester of pregnancy. METHODS: A comparative study, with each patient serving as her own control, was carried out on 10 primigravid women with 49--84 days amenorrhoea undergoing surgical termination of pregnancy. Each woman had two MRI scans of the uterus and cervix. The first scan was performed prior to administration of prostaglandins and the second scan 2.5--3 h following an 800 microg dose of misoprostol given vaginally. Cervical change was assessed by measurement of cervical length, transverse diameter of the cervix, diameter of the internal os and cervical stromal signal intensity. RESULTS: A significant difference in cervical length (P = 0.012), transverse diameter (P = 0.001) and diameter of the internal os (P = 0.008) was detected following the administration of misoprostol. In five women a significant change in one or both components of the cervical stromal signal was detectable and in five women no change could be demonstrated. CONCLUSION: MRI is capable of detecting changes in the physical parameters of the cervix following administration of prostaglandin. However, the changes detected in the stromal signal intensity are less consistent. The potential of MRI as a clinical tool to monitor cervical changes in a variety of clinical situations warrants further investigation.

Patient satisfaction with the management of infertility.

The objective of this study was to assess patient satisfaction with the investigation and initial management of infertility. A postal questionnaire survey was carried out of 1366 women attending outpatient clinics for the investigation and initial management of infertility at 12 hospitals throughout Scotland. The response rate to the questionnaire was 59% (806/1366). Overall, 87% of responders were satisfied or very satisfied with their care but a number of deficiencies were identified. Thirty-nine per cent had never been asked to bring their partner to the clinic and 86% felt they had not been given enough help with the emotional aspects of infertility. Forty-seven per cent felt they were not given a clear plan for the future and 23% of those who had been given drug treatments reported receiving little or no information about the treatment or possible side-effects. Overall, only a third had been given any written information and 78% expressed a wish for more written information. Women ranked 'the information and explanation given' and the 'attitude of the doctor at the clinic' highly in comparison to other aspects of their care, including 'help with the emotional aspects of infertility'. In general women were satisfied with their care but improvements may be made by giving more explanation and written information and by adopting a more couple-centred approach. Where resources allow, clinics should take steps to address the emotional aspects of infertility.

Smoking and female infertility: a systematic review and meta-analysis.

The high prevalence of smoking among women in their reproductive years continues to be a matter of concern. The negative effects of smoking on general health are well known, but smoking may also affect fertility. The objective of the present study was to perform a systematic review of the literature to determine whether there is an association between smoking and risk of infertility in women of reproductive age, and to assess the size of this effect. In the 12 studies used for this meta-analysis, the overall value of the odds ratio (OR) for risk of infertility in women smokers versus non-smokers was 1.60 [95% confidence interval (CI) 1.34-1.91]. Studies of subfertile women undergoing in-vitro fertilization (IVF) treatment also show a reduction in fecundity among women smokers. A meta-analysis of nine studies found an OR of 0.66 (95% CI 0.49-0.88) for pregnancies per number of IVF-treated cycles in smokers versus non-smokers. Despite the potential limitations of meta-analyses of observational studies, the evidence presented in this review is compelling because of the consistency of effect across different study designs, sample size and types of outcome. However, continued reassurance is needed that the calculated overall effect is not in fact due to confounding variables.

Cancer in women with infertility.

There has been increasing concern in recent years regarding a possible link between drugs given for infertility treatment and the subsequent risk of cancer, particularly ovarian cancer. Recent epidemiological studies reassure us that any effect, if present, is likely to be small, and does not affect women who conceive with such treatment.

Medical abortion or vacuum aspiration? Two year follow up of a patient preference trial.

OBJECTIVE: To describe and compare health outcomes two years after medical abortion or vacuum aspiration in women recruited into a patient preference trial during 1990 to 1991. DESIGN: Women recruited to the original, partially randomised study were contacted for assessment using a structured interview. SETTING: Grampian region of Scotland, UK. PARTICIPANTS: One hundred and forty women who had participated in a partially randomised study of first trimester abortion two years previously. INTERVENTION: Vacuum aspiration or medical abortion using mifepristone and gemeprost. MAIN OUTCOME MEASURES: Long-term general, reproductive and psychological health; acceptability of procedure; perceived value of choice of method of termination. RESULTS: There were no significant differences between women who had undergone medical abortion or vacuum aspiration two years previously in general, reproductive or psychological health. Almost all women placed a high value on the provision of choice of method of termination. There was a significant difference in perception of long term procedure acceptability among women who had been randomised to a method of termination. CONCLUSIONS: Women should have the opportunity to choose the method of termination. This opportunity will result in high levels of acceptability, particularly at gestations under 50 days of amenorrhoea.

PIP: In a comparative study conducted during 1990-91, 363 Scottish women with pregnancies of less than 64 days of gestation were given the option of selecting medical abortion with mifepristone/gemeprost or surgical vacuum aspiration abortion; those without a preference were randomly assigned to a method. There were no differences between groups in efficacy or medical complications at the 21-day postabortion follow-up. Medical abortion was associated with significantly more pain during the procedure, but not following hospital discharge, and its efficacy decreased with advancing gestation. At a median time interval of 26 months after the abortion, 140 women from the original cohort were reinterviewed to assess long-term acceptability. There were no significant differences between the medical and surgical abortion groups at long-term follow-up in their assessment of their current health status, the nature and incidence of subsequent morbidity requiring a doctor's care, consultations for psychiatric problems, or menstrual disorders. 9% of women who opted for surgical abortion and 11% who chose medical abortion indicated they would select a different method in the future. Vacuum aspiration remained significantly more acceptable than medical abortion among women who were randomly allocated to an abortion group. 97 women (69%) rated the opportunity to choose an abortion method as highly important, and 86-90% indicated a willingness to pay for the provision of such choice.

Laboratory techniques for semen analysis: a Scottish survey.

OBJECTIVE: To survey the techniques used by Scottish laboratories to undertake semen analysis in the context of the investigation of infertility. DESIGN: A telephone survey. SETTING/SUBJECTS: Laboratories in Scotland performing semen analysis. RESULTS: Thirty-one laboratories reported performing semen analysis for infertility. There was a lack of consistency in the instructions given to patients in several areas, including the period of abstinence prior to producing the specimen and the delivery of the specimen to the laboratory within an appropriate time after ejaculation. Only 19% of laboratories reported using a positive displacement pipette in the dilution of semen and only 26% used phase contrast microscopy for routine semen analysis. The minimum normal values quoted by laboratories for sperm concentration ranged from 20 x 10(6)/ml to greater than 50 x 10(6)/ml. The normal values quoted for sperm morphology ranged from at least 30% normal forms to at least 88% normal forms. Only 13% of laboratories participated in any form of internal or external quality control for semen analysis. CONCLUSIONS: Semen analysis is fundamental to the clinical work up of the infertile couple but, unlike most other laboratory investigations, it is not a standardised test in Scotland. Factors which are known to influence the results such as the advice given to patients about collecting specimens and the methods and equipment used by technicians vary widely. There is not even a consensus on the normal values quoted. This has implications for clinical decisions based on semen analysis and for future accreditation of laboratories.

Effect of mifepristone on folliculogenesis in women treated with recombinant FSH.

OBJECTIVE: To study the mechanism through which mifepristone interrupts folliculogenesis. DESIGN: Normally ovulating women undergoing donor intrauterine insemination (IUI) treatment were investigated during two menstrual cycles treated with gonadotrophins. In the first cycle (FSH cycle), the women were given 150 IU recombinant FSH (rFSH) s.c. on days 2, 4, 6, 8 and daily thereafter until the administration of hCG. During the second cycle (FSH + mifepristone cycle), the women received rFSH as above plus mifepristone tablets at a dose of 50 mg/day from cycle day 2 until the hCG injection. IUI was performed only in the FSH cycles. PATIENTS: Eleven normally ovulating women were studied. The women were used as their own controls during the cycle treated with rFSH only. RESULTS: Two women became pregnant during the FSH cycle and, therefore, data for comparison between the two cycles were available in nine women. In both cycles, only one follicle reached the preovulatory stage. However, during treatment with FSH + mifepristone the growth of the dominant follicle was temporarily arrested after day 8 of the cycle and ovulation was postponed by 2 days on average. Serum FSH values increased significantly in both cycles only during the daily administration of rFSH, i.e. towards the end of the experimental period when a normal growth of the follicle was re-established. On the day of hCG injection, an endogenous LH surge had already started in six of the nine cycles treated with FSH (67%) but in none of the FSH + mifepristone cycles despite the preovulatory oestradiol (E2) levels. Endometrial thickness during the follicular phase and serum E2 and progesterone concentrations during the luteal phase, although in the normal limits, were significantly lower in the FSH + mifepristone than in the FSH cycles. CONCLUSIONS: These results suggest that mifepristone arrests follicular development at a stage beyond the recruitment-selection point by delaying the growth of the dominant follicle. This is probably achieved through an effect of mifepristone on the ovary where it reduces the sensitivity of the selected follicle to FSH. Mifepristone may have a potential application for the inhibition of the LH surge in superovulation induction programmes.

Laparoscopic sterilisation: opinion and practice among gynaecologists in Scotland.

OBJECTIVES: 1. To produce a list of evidence-based criteria for good quality care relating to female laparoscopic sterilisation. 2. To assess the level of agreement with each criterion among gynaecologists in Scotland. 3. To obtain an overview of current sterilisation practice for comparison with the agreed criteria. DESIGN: 1. Agreement with criteria assessed by questionnaire survey; 2. Overview of current practice obtained by questionnaire survey and by casenote review. SETTING: Scotland. SAMPLE: 1. Questionnaire survey: all 132 consultant gynaecologists in NHS practice. 2. casenote review: 988 consecutive women sterilised in 12 representative hospitals. RESULTS: The response rate to the questionnaire survey was 94%. A list of 15 evidence-based criteria was produced, covering patient selection, information and counselling, techniques of tubal occlusion and timing of sterilisation. All 15 suggested criteria gained an overall balance of support among responding gynaecologists. Similar impressions of current practice were gained from the questionnaire survey and from the casenote review. Aspects of practice which measured up well to the agreed criteria included: only 6% of women sterilised were younger than 25 years of age; over 85% of casenotes included clear documentation that women had been counselled regarding failure rate and intended permanency; 88% of sterilisations were performed, or directly supervised by, a gynaecologist of consultant or senior registrar status; and only 2% of sterilisations were undertaken in combination with induced abortion. Aspects of practice which compared poorly with the agreed criteria, and for which recommendations for change have been made, included: only 22% of casenotes mentioned that the option of vasectomy had been discussed; only 30% of gynaecologists indicated that they provide locally produced information leaflets as an adjunct to counselling; four methods of tubal occlusion (including unipolar diathermy) were in use; and there were wide variations among hospitals in the use of day-case care, ranging from 19% to 99%. CONCLUSIONS: A list of criteria for good quality care in relation to sterilisation has been validated by agreement among Scottish gynaecologists. Current practice (as assessed by questionnaire survey and casenote review) has been compared with the criteria and some recommendations for change in practice have been made. Following dissemination of these results and recommendations, re-audit will be undertaken in order to identify any changes.

PIP: To facilitate the development of clinical criteria for laparoscopic sterilization, questionnaires were mailed to all 132 consultant gynecologists in the Scottish National Health Service and the medical records of 988 consecutive women undergoing sterilization at 12 representative hospitals were reviewed. Physicians were asked to rate their agreement with 15 statements related to patient selection, preoperative counseling, tubal occlusion techniques, and sterilization timing. The 123 respondents provided agreement scores ranging from 46% to 100%, but there was an overall pattern of support. Most controversial were criteria specifying that sterilization acceptors should be older than 25 years, the male partner should be present at counseling, and that interval sterilization is preferable. Physicians indicated a preference for the Filshie clip (59%) and Falope ring (29%). The record review revealed a low rate (6%) of sterilization among women under 25 years old, good documentation of counseling regarding the failure rate and intended permanency, a high proportion (88%) of procedures performed or directly supervised by senior gynecologists, and low utilization (2%) of combined abortion-sterilization procedures. On the other hand, the review identified minimal promotion (22%) of the option of vasectomy, low provision (30%) of patient information leaflets, continued use of unipolar diathermy, and low use of day case care. After dissemination of these criteria, a second case audit is planned to identify beneficial changes in practice.

Effect of mifepristone (RU486) on the pituitary response to gonadotrophin releasing hormone in women.

Mifepristone interrupts folliculogenesis in women but the mechanism is not clear. Previous studies have investigated the effect of this compound on gonadotrophin secretion and have provided conflicting results. To study further the effect of mifepristone on basal and gonadotrophin-releasing hormone (GnRH)-induced gonadotrophin secretion, 12 normally ovulating women were investigated during two consecutive menstrual cycles, comprising an untreated cycle (control) and a cycle treated with mifepristone. All women were treated with mifepristone on days 2-8 at the dose of 100 mg (group 1, eight women) or 10 mg per day (group 2, six women). Two women were treated with both regimens in two different cycles. On day 8 of both cycles, the women received two GnRH pulses of 10 micrograms each 2 h apart. Blood samples in relation to the first GnRH pulse were taken at-15, 0, 30, 60, 120, 150, 180 and 240 min. In group 1, the increase in luteinizing hormone (delta LH) in response to GnRH was significantly attenuated from 30 to 180 min, while the increase in follicle stimulating hormone (delta FSH) was attenuated only in response to the second GnRH pulse. No significant decrease in delta LH and delta FSH response to GnRH was seen during treatment with the 10 mg dose (group 2). In group 1, serum oestradiol and inhibin-A concentrations after day 8 were lower than in the control cycles and the LH peak was postponed by 7 days on average. Basal LH values increased significantly on day 8 in both groups, while FSH values did not change significantly compared with the control cycles. A significant increase in serum progesterone and cortisol values occurred during the treatment only in group 1. Mid-luteal values of inhibin-A were significantly lower in cycles treated with 100 mg mifepristone than in the control cycles. We conclude that the disruption of folliculogenesis by mifepristone cannot be explained by a decrease in basal FSH concentrations during the critical period of follicle recruitment and selection. It is possible that mifepristone exerts its effect at the level of the ovary. It is also suggested that progesterone during the follicular phase of the cycle may participate in the control of the self-priming action of GnRH on the pituitary.

PIP: In the UK and Greece, clinical researchers investigated 12 normally ovulating women during two consecutive menstrual cycles (control) and a cycle treated with oral mifepristone (case) on days 2-8 to determine the role of progesterone during the follicular phase of the menstrual cycle and the possible mechanism through which mifepristone interrupts folliculogenesis in women. 7 women received 100 mg mifepristone, and the other 5 women received 10 mg mifepristone. Treatment with 100 mg mifepristone/day during the first half of the follicular phase yielded a significant increase in the timing of the luteinizing hormone (LH) response to gonadotropin releasing hormone (GnRH) from 30 to 180 minutes. In fact, the weakened LH response occurred in both GnRH pulses, suggesting that mifepristone influenced both the releasable and reserve pool of LH in the pituitary gland. Mifepristone (100 mg) also weakened the response of follicle stimulating hormone (FSH) to the second GnRH pulse. 10 mg mifepristone did not have similar effects on the LH and FSH responses to GnRH, however. 100 mg mifepristone caused a reduction in serum estradiol and inhibin-A concentrations after day 8 (p 0.05) and postponed the LH peak by 7 days on average. Mid-luteal inhibin-A concentrations were lower in cycles treated with 100 mg mifepristone than in the control cycles. Both mifepristone doses increased basal LH secretion on day 8 (p 0.05). Basal FSH concentrations throughout the treatment periods were similar to those in controls, however. This suggests that the inhibitory effect of mifepristone on either the selection or further growth of the dominant follicle occurs within the ovary. These findings suggest that progesterone during the follicular phase may contribute to the control of the self-priming action of GnRH on the pituitary.

Identification of gonadotrophin surge-inhibiting factor (GnSIF)/attenuin in human follicular fluid.

Evidence from several laboratories suggests that the ovaries of many species produce a non-steroidal factor called gonadotrophin surge-inhibiting or attenuating factor (GnSIF) which may regulate the response of the pituitary to gonadotrophin-releasing hormone (GnRH) and as such, may modulate the timing and/or amplitude of the luteinizing hormone (LH) surge. We have recently isolated a candidate GnSIF from porcine follicular fluid (PFF). Porcine GnSiF is a 69 kDa protein which has undetectable inhibin and follistatin immunological and biological activity. The present study was designed to purify and identify GnSIF from human follicular fluid. GnSIF activity was measured as suppression of GnRH-stimulated LH secretion from rat pituitary cells in primary culture. Human follicular fluid (approximately 500 ml) was recovered from patients undergoing in-vitro fertilization (IVF). GnSIF was purified by heparin-sepharose, Q-sepharose, S-sepharose, and hydrophobic interaction chromatography followed by isoelectric focusing. Gel electrophoresis and Western blot were used to identify human GnSIF and compare it with porcine GnSIF. Using these steps, we obtained a highly-purified preparation of GnSIF that manifests in-vitro bioactivity and chromatography characteristics similar to those observed for porcine GnSIF and that hybridizes with a porcine GnSIF antibody. Following treatment with human chorionic gonadotrophin/human menopausal gonadotrophin (HMG/HCG), human follicular fluid contained roughly 25% of the GnSIF (per mg protein) present in porcine follicular fluid. We conclude that GnSIF is present in human follicular fluid and may participate in the regulation of gonadotrophin secretion in this species.

Effect of follicle stimulating hormone or human chorionic gonadotrophin treatment on the production of gonadotrophin surge attenuating factor (GnSAF) during the luteal phase of the human menstrual cycle.

OBJECTIVE: Although there is much in-vivo evidence for the existence of a gonadotrophin surge attenuating factor (GnSAF), its source and identity remain unknown. We have studied the control of GnSAF production by FSH and hCG during the luteal phase of the cycle. DESIGN: Normally cycling women were investigated in three cycle. Starting on day 5 after the midcycle LH peak, the women received i.m. injections of placebo (1st cycle control), hCG at a dose of 750 IU per day (2nd cycle) and FSH at a dose of 225 IU per day (3rd cycle) for five consecutive days. The response of LH to a single i.v. dose of 10 microg GnRH (GnSAF bioactivity) was investigated several times during the experimental period. PATIENTS: Six normally ovulating women with long-standing unexplained infertility were studied. The women were used as their own controls during the cycle treated with placebo. MEASUREMENTS: Pituitary response to GnRH was calculated as the net increase in LH at 30 minutes (deltaLH) above the basal value. RESULTS: Serum concentrations of FSH and hCG increased significantly during the second and 3rd cycles respectively. Compared with the control cycles, deltaLH was significantly attenuated as early as 12 hours from the onset of FSH injections. In contrast, basal concentrations of oestradiol (E2) and immunoreactive inhibin started to increase 48 hours after the first injection of FSH, while progesterone values remained similar to those in the controls. During treatment with hCG, no attenuation was seen in deltaLH values, while those of E2, progesterone and inhibin showed a significant increase. CONCLUSIONS: These results demonstrate that during the luteal phase of the human menstrual cycle, FSH, but not LH, stimulates the production of gonadotrophin surge attenuating factor. It is suggested that the source of gonadotrophin surge attenuating factor at that stage of the cycle is a cohort of small follicles rather than the corpus luteum.

A prospective clinical study of the relationship between the computer-assisted assessment of human semen quality and the achievement of pregnancy in vivo.

The objective of this study was to examine the clinical predictive value for the achievement of pregnancy in vivo of the assessment of human semen quality by computer-assisted semen analysis using the Hamilton-Thorn Motility Analyser (HTM-S), alongside classic World Health Organization (WHO) techniques. A prospective follow-up study of 303 couples attending a regional infertility clinic providing tertiary level services to the population of a single geographical region was undertaken. Couples attending the infertility clinic, in whom the female partner was normal on conventional investigations (history, examination, evidence of ovulation, laparoscopy), were studied. After initial assessment, couples were followed for a median of 15 months and treatment-independent pregnancies observed and related to the results of semen assessment. During the period of follow-up, the treatment-independent pregnancy rate was 52%. Several measures of semen quality, determined both manually and by the HTM-S, were found to be predictive of the achievement of pregnancy and were related to the time taken to conceive. Couples who conceived had higher sperm concentrations and motilities, determined both manually and by the HTM-S, as well as differences in sperm head morphometry and sperm velocity determined by the HTM-S. Using multiple logistic regression, the prognostic accuracy of the HTM-S alone was similar to manual techniques, although data from the computer assisted sperm analysis system were preferred. Using proportional hazards regression, several variables were related to the achievement of pregnancy, particularly morphometry and motility. It was concluded that a strong case can be made for the introduction of automated assessment of human semen in routine service andrology laboratories.

"Benign" metastasizing pleomorphic adenoma. A case report and review of literature.

A case of a 34-year-old man with a pathologic fracture through a lytic lesion in the left glenoid is presented. The results of a needle biopsy of the lesion showed a benign pleomorphic adenoma. Sixteen years previously, the patient had a pleomorphic adenoma of the parotid gland. Histology of the initial tissue and the needle biopsy specimen were identical. The patient developed metastasis without any local recurrence of the initial tumor. When evaluating a patient with a lytic lesion of bone with a history of a benign pleomorphic adenoma of the salivary gland, a metastasis should be considered.

A comparison of medical abortion (using mifepristone and gemeprost) with surgical vacuum aspiration: efficacy and early medical sequelae.

A total of 363 women undergoing legal abortion at < 63 days of amenorrhoea were allocated by a patient-centered, partially randomized study design to undergo medical abortion (using mifepristone 600 mg followed 48 h later by gemeprost 1 mg vaginal pessary) or vacuum aspiration (performed under general anaesthesia). The aim of the study was to compare the efficacy and complications of the two procedures. Main outcome measures included efficacy rates, medical complications within 21 days of abortion and unplanned family doctor consultation rates within 8 weeks following abortion. Sequelae such as pain, vaginal bleeding and recovery time were assessed by the change in haemoglobin level, the time taken to return to work or normal activity and the analgesic use. Results were gestation-related; at 50 days of amenorrhoea there was little to choose between the two procedures. At 50-63 days of amenorrhoea medical abortion becomes more painful and less effective, whereas vacuum aspiration retains high tolerance and efficacy. Women who are unsure which method to use are likely to find vacuum aspiration more acceptable at longer gestations.

PIP: In Aberdeen, Scotland, researchers compared the efficacy rate of medical abortion with that of vacuum aspiration and examined their complications and the nature and incidence of short-term sequelae. All 363 pregnant women had amenorrhea for less than 63 days. The medical abortion procedure consisted of administration of 600 mg mifepristone followed by 1 mg gemeprost (vaginal pessary) 48 hours later. Women who underwent medical abortion at less than 50 days gestation were less likely to experience pain than those who underwent medical abortion between 50 and 63 days gestation (mean pain related index [PRI] scores, 20.5 vs. 25.5, p = 0.04 and analgesia during inpatient treatment, 43% vs. 63%; p = 0.02). Medical abortion was less effective at 50-63 days gestation than at less than 50 days gestation (complete abortion, 98% vs. 92.6%). 90% of women requiring curettage after medical abortion were at 50-63 days gestation. Gestation affected neither pain nor efficacy rates of vacuum aspiration, however. At follow-up 16 days after the procedure, the significant differences in the medical sequelae of the 2 procedures during and immediately after abortion disappeared. The short-lived sequelae did not greatly affect recovery times. For example, even though women who underwent vacuum aspiration required more time off work than those who underwent medical abortion (2.5 vs. 1.2 days; p = 0.007), the return of normal daily activities was essentially the same for both groups (0.6-1.3 vs. 0.8-1.5 days). These results suggest that at gestations of less than 50 days, the 2 procedures are equally effective and have similar 0-21 day complication rates. On the other hand, at 50-63 days gestation, medical abortion becomes more unpleasant and its efficacy begins to diminish. In conclusion, at higher gestations, women who do not prefer one method over another will probably find vacuum aspiration more acceptable than medical abortion.

Modulation of the action of gonadotrophin surge-attenuating factor by gonadotrophin-releasing hormone.

Gonadotrophin surge-attenuating factor (GnSAF) is a putative non-steroidal ovarian factor which attenuates the luteinizing hormone (LH) surge in superovulated women through the reduction of the pituitary response to gonadotrophin-releasing hormone (GnRH). The mechanism of action of GnSAF on gonadotrophin secretion was further studied by investigating six normally ovulating women in two cycles--a spontaneous and a follicle-stimulating hormone (FSH)-treated cycle. The response of the pituitary to five consecutive pulses of GnRH was investigated in late follicular phase (follicle size 15 mm) of both cycles. GnRH pulses, 10 micrograms each, were injected i.v. every 2 h and LH was measured in blood samples taken before and 30, 60 and 120 min after each pulse. FSH was injected daily at the fixed dose of 225 IU starting on cycle day 2. Peak values of LH increment occurred 30 min after each pulse. However, maximal LH increment occurred in both cycles after the second GnRH dose. In the FSH cycles the response of LH to the first three pulses was significantly attenuated compared with the spontaneous cycles, while the response to the fourth and fifth pulses was similar in the two cycles. In both cycles, LH increment 30 min post GnRH (net increase above the previous value) was similar after the fourth and fifth pulses. Serum concentrations of oestradiol and immunoreactive inhibin, although higher in the FSH cycles, remained stable throughout the GnRH experimental period in both cycles. These results demonstrate that multiple submaximal doses of GnRH can override the attenuating effect of GnSAF on LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of an increase in FSH on the production of gonadotrophin-surge-attenuating factor in women.

Gonadotrophin-surge-attenuating factor (GnSAF) is a putative nonsteroidal ovarian factor that is produced by FSH and that attenuates the LH surge in superovulated women. To study further the role of FSH in the production of GnSAF, 12 normally ovulating women were divided into two groups and investigated during two cycles: a cycle treated with placebo (control) and a cycle treated with FSH. In group 1 (n = 6), placebo (2 ml 0.9% normal saline) or FSH (450 iu) was injected i.m. on day 2 of the cycle (09:00 h). In group 2 (n = 6), placebo (2 ml 0.9% normal saline) or FSH (225 iu) was injected on the day (09:00 h) on which the dominant follicle was 14-15 mm in diameter, as measured by ultrasound (i.e. after the pituitary had been primed by endogenous oestrogen for several days). The response of LH over 30 min (delta LH) to an injection of 10 micrograms LHRH i.v. (bioassay for GnSAF in vivo) was investigated once a day in group 1, and 4, 8, 12 and 24 h after the injection of placebo or FSH in group 2. In group 1, delta LH was significantly attenuated 12 h after treatment with FSH compared with the control cycles, while serum oestradiol concentrations increased 24 h after the injection of FSH. The decrease in delta LH lasted for the period when the FSH concentration was increased (3 days). A significant decrease in the basal concentration of LH was correlated with the increase in the oestradiol concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of women with mild and moderate cervical dyskaryosis.

OBJECTIVE: To compare the outcomes in women with mild and moderate dyskaryosis after increasing periods of surveillance and thereby to define a rational protocol for managing such women. DESIGN: Prospective study with randomisation of women to one of four treatment groups, each with a different period of surveillance; one group in which the women were given immediate treatment and three other groups in which the women were under surveillance for six, 12, and 24 months. SETTING: A dedicated colposcopy clinic in Aberdeen, Scotland. SUBJECTS: 902 women who presented with a mildly or moderately dyskaryotic smear for the first time. INTERVENTIONS: Cytological and colposcopic examinations at intervals of six months until the allocated period of surveillance was completed, at which time biopsy was performed. Women with severe dyskaryosis were withdrawn from surveillance and a biopsy was performed. MAIN OUTCOME MEASURES: The histological findings after punch biopsy or large loop excision of the transformation zone, and the trends in cytological appearances of serial cervical smears. RESULTS: 793 women completed the study. In all, 769 women had an adequate final smear, of which 197 were normal cytologically, 328 were still mildly or moderately dyskaryotic, and 244 were severely dyskaryotic. Seventeen of the 67 (25%) women with one repeat smear showing non-dyskaryosis had cervical intraepithelial neoplasia grade III compared with only one of the 31 (3%) women with no dyskaryosis in four repeat cervical smears (P < 0.0001). None of the women had invasive cancer. Of 158 women whose index smear showed mild dyskaryosis and who were allocated to the group under surveillance for two years, only 40 had not defaulted or still had dyskaryotic smears by the end of the two years. CONCLUSION: Cytological surveillance, although safe, is not an efficient strategy for managing women with mildly abnormal smears. Women with any degree of dyskaryosis in a smear should be referred for colposcopy.

Effect of follicle stimulating hormone treatment on the pituitary response to luteinizing hormone-releasing hormone in post-menopausal women.

To study the role of exogenous follicle stimulating hormone (FSH) in the attenuation of luteinizing hormone (LH) response to luteinizing hormone-releasing hormone (LHRH) during ovulation induction in women, 10 healthy post-menopausal women were treated with FSH (225 IU/day) for 5 days and normal saline (2 ml/day) for another 5 days. The two regimens were given consecutively in a 10 day experiment. The regimen for the first 5 days was randomly chosen and was given to the women in an alternate way. The response of LH to an i.v. injection of 10 micrograms LHRH was investigated twice on day 1 (i.e. before the onset of treatment and 12 h later) and once on days 2, 5 and 10 of the experiment (0900 h). Basal FSH and LH values before the onset of treatment on day 1 were similar in the five women who started with the saline and the five who started with the FSH regimen. Basal FSH values increased significantly during treatment with FSH, while LH and oestradiol values remained unchanged throughout the whole experiment. LH increment 30 min post-LHRH did not change significantly either during the first 24 h or during the whole experiment regardless of the starting regimen. These results demonstrate that in post-menopausal women the response of LH to LHRH is not affected by exogenous administration of FSH. It is suggested that exogenous FSH does not show activities on gonadotrophin secretion similar to those ascribed to a gonadotrophin surge attenuating factor.

Assessment of the conventional criteria of semen quality by computer-assisted image analysis: evaluation of the Hamilton-Thorn motility analyser in the context of a service andrology laboratory.

A comparative assessment of the conventional criteria of semen quality (sperm concentration, motility and morphology) was undertaken by standard laboratory techniques and by means of a computer-assisted image analysis system (the Hamilton-Thorn HTM-S 2030) in an open prospective study, in the context of a service andrology laboratory. A total of 1435 semen samples submitted by couples in the course of routine infertility investigations were examined by both methods, and the results compared. It was observed that the method did not provide comparable data on semen quality, either in respect of sperm concentration or graded motility, while the morphometric data generated by the HTM-S did not appear to be related to conventional morphology assessment. The clinical value of such systems in the assessment of the classical determinants of semen quality requires formal assessment in properly conducted large scale prospective studies.