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Background:: Lateral hindfoot pain in patients with flatfoot deformity is frequently attributed to subfibular impingement. It remains unclear whether this is primarily due to bony or soft-tissue impingement. No studies have used weight-bearing CT scans to evaluate subfibular impingement., Methods:: Patients with posterior tibial tendonitis were retrospectively searched and reviewed. Subjects had documented flatfoot deformity, posterior tibial tenderness, weight-bearing plain radiographs, and a weight-bearing CT scan. CT scans were evaluated for calcaneofibular impingement on the coronal view and talocalcaneal impingement on the sagittal view. The distance between these structures was measured, along with the sinus tarsi volume. In the second part of this study, 6 normal volunteers underwent weight-bearing CT scans on a platform that held both feet in 20 degrees of varus, followed by 20 degrees of valgus. The same measurements were performed., Results:: Thirty-five percent of flatfoot patients with posterior tibial tendonitis had bony impingement between the fibula and calcaneus on the coronal view. Thirty-eight percent had bony impingement between the talus and calcaneus on the sagittal view. Subjects with bony impingement based on CT scan had significantly higher talonavicular abduction angles on plain radiographs than those without impingement. Sinus tarsi volume decreased by more than half when the subtalar joint moved from varus to valgus in normal controls., Conclusion:: Bony subfibular impingement in patients with flatfeet was less common than previously reported. Accurate diagnosis of bony impingement may be useful for surgical decision-making., Level of Evidence:: Level III, retrospective comparative study.

Background: Unstable ankle syndesmosis injuries are common, and the optimal surgical fixation is controversial. The two main options for stabilization of syndesmotic injuries are suture button fixation and screw fixation. Suture button fixation has a higher initial cost, but may have a lower hardware removal rate. The purpose of this study was to compare the costs of syndesmotic fixation., Methods: A cost analysis was performed at a single university-affiliated hospital. Variables included the number of suture buttons, the number and type of syndesmosis screws used, and the frequency of hardware removal and operative time required for hardware removal. There were four clinical scenarios evaluated: (A) one suture button versus one cortical screw; (B) two suture buttons versus two cortical screws; (C) one suture button versus one locking screw; (D) two suture buttons versus two locking screws. Suture button removal rate was assumed to be 0% in the analysis., Results: Cost equivalence was achieved at an 18 to 53% syndesmotic screw removal rate depending on the fixation construct used and the amount of time required for hardware removal. When the syndesmosis screws were removed 100% of the time, suture button fixation was more economical by $85,000-$194,656 per 100 ankles. When hardware was never removed, suture button fixation was more expensive by $169,844-$295,500 per 100 ankles., Conclusion: This study demonstrates that the costs associated with syndesmosis fixation are more dependent on the rate of hardware removal than the type of hardware utilized. Routine removal of syndesmosis screws is clearly less economical than suture button fixation.

Background: The aim of this study was to investigate the association of total duration of oral contraceptive usage with time to conception., Methods: This was a prospective study of 8497 planned pregnancies drawn from a population that recruited 85% of eligible couples in South-West England who were expecting a baby in a 21 month period. Self-completion questionnaires were administered at 18 weeks gestation to ascertain parity, paternity, co-habitation, use of the contraceptive pill, smoking and alcohol status, educational achievement, height, weight and time taken to conceive. Logistic regression was used to identify factors independently related to conception in < or =12 months., Results: Of the participants, 74% conceived in < or =6 months, 14% in 6-12 months and 12% after 1 year. Previous prolonged oral contraceptive usage was statistically significantly associated with a decreased risk of delayed conception. Prolonged use of oral contraception was also associated with improved fecundity independent of other factors. Selection bias due to particularly fertile women using oral contraceptives is unlikely because similar odds ratios were calculated for nulligravid women., Conclusions: Women who have prolonged use of oral contraceptives might be reassured that they will not be disadvantaged in terms of time taken to achieve conception.

Problem: To measure and compare concentrations of total and free glucocorticoids with oocyte fertilizing capacity in the follicular fluid (FF) of women with minimal-mild endometriosis and tubal damage., Method of Study: Follicular fluid was collected from individual periovulatory follicles during oocyte retrieval for in vitro fertilization (IVF) in natural cycles. Total and free levels of cortisol and cortisone were measured using specific radioimmunoassays after chloroform extraction., Results: Cortisol concentrations in women with minimal-mild endometriosis were significantly lower compared with controls (women with tubal infective damage) (258 versus 328 nmol/L, P < 0.02). There was no correlation between total or free concentrations of cortisol or cortisone and the fertilization capacity of the oocyte., Conclusions: Total cortisol levels are lower in the follicles of women with endometriosis. Our findings provide further evidence of follicular dysfunction contributing to the subfertility associated with minimal-mild endometriosis.

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 <40 years of age were invited to participate in a twin centre prospective double blind randomized placebo controlled study. A total of 290 patients were recruited and computer randomized using sealed envelopes to receive either 1 mg dexamethasone (n = 145) or placebo tablets (n = 145) in addition to a standard long protocol gonadotrophin-releasing hormone analogue with gonadotrophin stimulation regime., Results: A significantly lower cancellation rate for poor ovarian response was observed in the dexamethasone group compared with controls (2.8 versus 12.4% respectively, P < 0.002). Further comparisons between the dexamethasone group and controls were made of median fertilization rates (60 versus 61% respectively, NS), implantation rates (16.3 versus 11.6% respectively, NS) and pregnancy rate per cycle started (26.9 versus 17.2%, NS). The benefit was apparent in patients both with polycystic and normal ovaries., Conclusion: Low dose dexamethasone co-treatment reduces the incidence of poor ovarian response. It may increase clinical pregnancy rates and should be considered for inclusion in stimulation regimes to optimize ovarian response.

The experimental group consisted of men from 81 couples waiting for in vitro fertilization (IVF), about half of whom had sperm dysfunction defined by a negative post-coital test. A diagnostic semen sample was subjected to a hamster oocyte penetration test (HOPT) after stimulation of the acrosome reaction with A23187 +/- pentoxifylline and to computerized sperm motility measurements (CASA) as well as conventional semen analysis according to the WHO protocol. Logistic regression was used to identify parameters that predicted the probability of achieving four or more viable embryos at IVF among the 65 couples from whom four or more oocytes were collected. The number of oocytes available and whether the woman had previously been pregnant (ever pregnant) were important factors but once these had been taken into account a number of sperm parameters had additional predictive power. The most useful of these were the percentage sperm static (CASA) or the percent sperm progressively motile (conventional semen analysis) in the Percoll preparation. A model incorporating the number of oocytes collected, ever pregnant and percentage sperm static achieved 85% correct prediction of outcome in the experimental dataset but only 62% correct prediction in an independent set of 280 IVF cycles. The percentage of hamster oocytes penetrated was a significant predictor but had no advantage over simple motility measurements. The results illustrate the difficulty of basing a prognosis for achieving satisfactory fertilization in IVF on the properties of spermatozoa.

Objective: To determine whether passive as well as active smoking by women or smoking by men is associated with delayed conception, after adjustment for confounding factors., Design: Population study of couples expecting a baby. Logistic regression was performed to identify factors associated with delayed conception., Setting: The Avon Health Authority area, United Kingdom., Patient(s): All couples expected to deliver between April 1991 and December 1992., Intervention(s): Questionnaires administered early in pregnancy., Main Outcome Measure(s): Time taken to conceive, categorized as <6 months, 6-11 months, 1-3 years, and >3 years., Result(s): After correction for confounding factors, delayed conception was statistically significantly associated with both active smoking by the woman (odds ratio [OR] 1.23 [95% CI 0.98-1.49] for > 6 months and 1.54 [95% CI 1.19-2.01] for >12 months) and her exposure to passive smoking (OR 1.17 [95% CI 1.02-1.37] and 1.14 [95% CI 0.92-1.42]) compared with women with no exposure to tobacco smoke (referent). Heavy smoking by men was independently associated with delayed conception. In active smokers, the effect increased with the number of cigarettes., Conclusion(s): Smoking by men and passive and active smoking by women are associated with delayed conception.

Controversy about the value of the post-coital test (PCT) has prompted us to re-analyse data from 207 couples, originally studied between 1982 and 1983, with at least 12 months' infertility at presentation, complete diagnostic information and exclusion of female factors, to clarify the effect of duration of infertility on the prediction of conception. In couples with less than 3 years infertility and a positive PCT, 68% conceived within 2 years compared with 17% of those with a negative result. After 3 years, corresponding rates were 14% and 11%. The relative risks of conception [95% confidence interval (CI)] calculated using the Cox's proportional hazards model were 0.23 (0.12-0.43) for a negative PCT (reference positive PCT) and 0.25 (0.13-0.51) for more than 36 months infertility (reference 12-23 months). Semen analysis had no extra predictive power given the duration of infertility and the PCT. The PCT is an effective predictor of conception where defined female causes of infertility are absent and duration of infertility is less than 3 years. Once infertility is prolonged (beyond 3 years) the conception rate is low even with a positive test because a large proportion of couples remaining childless so long have true unexplained infertility. Use of the PCT will enable clinicians to allocate scarce, expensive and invasive resources effectively.

Data relating serum oestradiol concentration to follicle size in unstimulated cycles are lacking. We provide precise data on serum concentrations expected for any follicle diameter (FD) in the mid- to late follicular phase. Infertile women (n = 35) with apparently normal ovulatory cycles were studied in detail in 128 unstimulated monofollicular cycles leading to IVF. Using mathematical modelling to account for repeated cycles in the same woman, the relationship between serum oestradiol and FD was explored and reference ranges for serum oestradiol at individual FD were calculated. Serum oestradiol concentrations [number of patients, geometric mean, 95% confidence interval (CI)] at the onset of the LH surge were higher in 'fertilized' cycles (73, 1279, 1180-1378 pmol/l) compared with 'unfertilized' cycles (31, 1055, 929-1197 pmol/l, P: = 0.008) and 'no oocyte' cycles (24, 1064, 922-1227 pmol/l, P: = 0.03) respectively. In 'fertilized' cycles, oestradiol concentrations rose exponentially with FD and for each size of follicle the oestradiol distribution was skewed. Functional oocyte competence varied in apparently normal ovulatory cycles and was correlated with pre-ovulatory serum oestradiol but not FD. Serum oestradiol varies within wide limits for maturing follicles of any given diameter prior to the onset of the LH surge.

The impact of male age on fecundity remains controversial. Here, a large population study was used to investigate the effect of paternal age on time to conception. All couples in the Avon Health district expecting a baby between 1 April 1991 and 31 December 1992 were eligible. Questionnaires completed by both the man and the woman at 18 weeks gestation covered specific fertility factors, e.g. parity, paternity, cohabitation and oral contraception; and non-specific factors, e.g. educational achievement, housing, cigarette smoking, alcohol consumption, obesity. Logistic regression was used to identify factors independently related to conception in < or =6 or < or =12 months. Of 8515 planned pregnancies, 74% were conceived in < or =6 months, 14% in the second 6 months and 12% after more than a year. Nine variables, including the age of the woman, were independently related to time to conception. After adjustment for these, the likelihood of conception within 6 or 12 months was lower in older men. Compared to men <25 years old, the adjusted odds ratios (95% confidence interval) for conception in < or =12 months were 0.62 (0.40, 0.98), 0.50 (0.31, 0.81) and 0.51 (0.31, 0.86) in men aged 30-34, 35-39 and > or =40 years respectively.

Objective: To further elucidate cortisol metabolism in the follicular microenvironment at the time of oocyte retrieval, the presence of 11beta-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 11beta-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 11beta-HSD mRNA. Expression of mRNA is greatest in cumulus cells. Type 1 11beta-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.

Significant association between endometriosis, including minor endometriosis, and infertility (or strictly subfertility) is shown by prevalence studies, but a causal relationship has not been established. This review focuses on evidence for pituitary-ovarian dysfunction as a cause for the subfertility. A methodological problem is lack of fertile controls with endometriosis. Group comparison with tubal infertility cases as controls have demonstrated: impaired follicular growth, reduction in circulating oestradiol concentrations during the pre-ovulatory phase and of oestradiol and progesterone during the early luteal phase, and disturbed luteinizing hormone (LH) surge patterns. Reduction in LH concentrations in pre-ovulatory follicular fluid has also been found, and granulosa cells collected at the same time have demonstrated impaired steroidogenic capacity in vitro, but these were not consistently proven findings. Pooled data from published studies show significantly reduced oocyte fertilization rates (49%) compared with controls (69%), even after maximal stimulation with exogenous follicle stimulating hormone (FSH) and human chorionic gonadotrophin (HCG) (54 versus 69%). The implantation rate is also slightly (though significantly) reduced (11 versus 13%). The findings suggest an inherent disorder of follicular function, with LH surge impairment probably being a secondary phenomenon. The resulting reduction in the chance of fertilization of the oocyte would contribute substantially to the subfertility associated with endometriosis. It seems that the benefit of in-vitro fertilization is gained through the excessive number of oocytes obtained by stimulation.

Objective: To determine whether alterations in preovulatory follicular fluid (FF) levels of LH, FSH, and steroids are associated with the probability of fertilization., Design: Retrospective analysis of prospective study results., Setting: Reproductive medicine clinic of a university teaching hospital., Patient(s): Infertile women, with unstimulated, apparently regular cycles in an IVF research program., Intervention(s): Measurement of preovulatory FF levels of LH, FSH, E2, and P and serum LH levels by fluoroimmunometry., Main Outcome Measure: Oocyte fertilization., Result(s): There were 84 transferable embryos (rate of normal fertilization and cleavage, 67%), and 41 oocytes (33%) failed to fertilize. Analysis of the matched FF showed that the median concentration of FF LH was significantly higher for cleaving embryos than for unfertilized oocytes (14.6 vs. 10.4 IU/L). Serum LH concentrations were similarly higher in cycles with cleaving embryos. There were no statistically significant differences in FF concentrations of FSH, E2, or P in the two groups., Conclusion: Reduced preovulatory FF LH levels are associated with impaired fertilization of oocytes in vitro, despite normal FF FSH and steroid levels.

There is growing evidence that the pathogenic effects of bacterial vaginosis may not be confined to the lower genital tract. Possible associations with infertility and effects on fertilization and implantation were studied in patients undergoing in-vitro fertilization (IVF) treatment. High vaginal swabs taken at the time of oocyte collection were assessed by Gram staining. The prevalence of bacterial vaginosis and of intermediate and normal flora in 301 patients was 25.6, 14.0 and 60.4% respectively. Bacterial vaginosis was more prevalent in patients with tubal (31.5%, n = 149) compared with non-tubal (19.7%, n = 152) infertility (odds ratio (OR) 1.87, CI 1.11-3.18, P = 0.02). Bacterial vaginosis did not have an adverse effect on fertilization rate. Further, no significant difference in implantation rates was seen when comparing bacterial vaginosis (15. 8%, OR 1.03, CI 0.66-1.61) and intermediate flora (13.1%, OR 0.82, CI 0.45-1.52) with normal flora (15.5%). Though confidence intervals around the observations were relatively wide, the findings suggest that routine screening for bacterial vaginosis in the hope of improving the success of IVF treatment is not justified. The prevention of complications in pregnancy associated with bacterial vaginosis might be a more relevant indication for screening at the time of IVF treatment, in particular patients with tubal disease, if treatment were shown to be effective for that particular purpose. However, antibiotic treatment before IVF has been shown to be positively disadvantageous for IVF by encouraging other organisms.

Washed sperm suspensions from 64 out of 89 (72%) randomly selected infertility patients produced detectable reactive oxygen species (ROS) compared to 17 out of 67 (25%) prospective semen donors (p < 0.01, Chi-square test). Among patients, the median sperm concentration in ejaculates which yielded sperm suspensions that generated detectable levels of ROS was lower than in those which did not: 36.2 (15.63-57.64) vs. 71.5 (22-108) x 10(6)/mL, respectively (median (interquartile range), p < 0.05, Kruskal-Wallis test). In samples that produced ROS, the basal rate of production and the rates after stimulation with 50 mumol N-formyl met leu phe (N-FMLP) l-1 or with 100 nmol phorbol 12-myristate 13-acetate (PMA) l-1 were significantly and inversely correlated with sperm concentration in the ejaculate (r = -0.43, -0.41 and -0.35, respectively, p < 0.01 Spearman's rank correlation). The rate of ROS production showed no relationship to the motility of spermatozoa in semen, whether evaluated visually or via computer assisted semen analysis. However, there was a significant negative correlation (r = -0.370) between the motile, normal sperm concentration (MNSC) and basal ROS production, and when stimulated with N-FMLP (r = -0.311) or with PMA (r = -0.249) (all p < 0.05). In patient samples that generated detectable ROS, the ability of the spermatozoa to retain motility for 24 h after preparation on a 40/80% Percoll gradient was negatively correlated with basal ROS production (r = -0.310, p < 0.05). ROS production was also related to the outcome of in vitro sperm mucus penetration tests. Unstimulated levels of ROS production showed a significant (p < 0.05), negative correlation with the number of progressively motile spermatozoa present in mucus after 15 (r = -0.379) and 60 (r = -0.362) min. These results suggest that sperm samples with increased ROS tend to have poor semen quality and reduced performance in a number of routine, diagnostic sperm function tests.

The aim of this study was to evaluate the lipoprotein profile in women with hyperprolactinaemic amenorrhoea and to establish whether effective dopamine agonist therapy might have a beneficial effect. Blood samples were collected from women with hyperprolactinaemic amenorrhoea and from controls matched for age, body mass index and smoking. Follow-up blood samples were collected from women on dopamine agonist therapy as treatment for their hyperprolactinaemia. Plasma cholesterol, high density lipoprotein cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein cholesterol, triglycerides, serum oestradiol and prolactin were measured. No statistically significant differences were found in the lipoprotein profile of the patient (n = 15) and control (n = 15) groups. During treatment with the dopamine agonist, bromocriptine (n = 9), significant reduction in total cholesterol [4.87 (3.98-5.87) versus 5.60 (4.55-6.61) mmol/l, P = 0.024] and LDL cholesterol [3.22 (2.01-4.23) versus 3.72 (2.59-4.93) mmol/l, P = 0.033] was noted. We conclude that beneficial alterations in the lipoprotein profile may occur in response to effective dopamine agonist therapy, presumably as a consequence of return of ovarian function and alleviation of oestrogen deficiency. Women with hyperprolactinaemic amenorrhoea should be encouraged to take effective therapy to improve their lipoprotein profile and potentially reduce their cardiovascular risk.

This article has provided outcome-based evidence using easily understood graphic representation of cumulative pregnancy rates whenever possible for the methods used to investigate and treat female infertility. A scheme of basic routine investigations in specialist practice is developed and clear guidance provided on the choice of treatment for each couple.

This study aims to determine the relative contribution of oocyte and/or sperm dysfunction to the reduction of fertilization rates in vitro in cases of minor endometriosis and prolonged unexplained infertility. The results of in-vitro fertilization (IVF) treatment with ovarian stimulation have been compared between couples with the above conditions and women with tubal infertility (as control for oocyte function) and the use of donor spermatozoa (as control for sperm function). Fertilization and cleavage rates using husband's spermatozoa were significantly reduced in endometriosis couples (56%, n = 194, P < 0.001) and further significantly reduced in couples with unexplained infertility (52%, n = 327, P < 0.001) compared with tubal infertility (60%, n = 509). Using donor spermatozoa the rates were the same as using husband's spermatozoa in tubal infertility (61%, n = 27) or endometriosis (55%, n = 21) but significantly though only partly improved with unexplained infertility (57%, n = 60, P < 0.02). In unexplained infertility, a significantly increased proportion of couples experienced complete failure of fertilization and cleavage in a cycle (5-6% versus 2-3%). However, complete failure was not usually repetitive, and the affected couples did not account for the overall reduction in fertilization and cleavage rates, which remained significantly lower in the rest of the unexplained and endometriosis groups. Implantation and pregnancy rates appeared similar in all groups. The benefit of IVF treatment in cases of minor endometriosis and prolonged unexplained infertility is due to superabundance of oocytes obtained by stimulation. The reduction in natural fertility associated with endometriosis appears to be at least partly due to a reduced fertilizing ability of the oocyte. In unexplained infertility, there is distinct impairment due to otherwise unsuspected sperm dysfunction but probably also oocyte dysfunction.

Objective: To determine the diurnal variation in the onset of the preovulatory LH surge in women., Design: Prospective open cohort study., Setting: University hospital research program., Patient(s): Thirty-five women with infertility resulting from tubal damage that was associated with minor endometriosis or with infertility of prolonged unexplained etiology., Intervention(s): Women underwent transvaginal ultrasonography and serum E2 estimation daily during monitored cycles before unstimulated natural cycle IVF: exogenous gonadotropins were not administered., Main Outcome Measure(s): Serum E2 concentration, follicle diameter, and endometrial thickness., Results: Of 169 cycles. 155 progressed to an ovulatory LH surge, of which 146 occurred within 8 hours of assessment of the outcome measures. The relationship between follicle diameter and E2 was weak, but an abnormal value for one always was countered by a normal value for the other., Conclusions: Most women begin the preovulatory LH surge between midnight and 8:00 A.M., but with no particular variation by day of the week. The relationship between follicle size and serum E2 is not sufficiently strong to predict the LH surge confidently on the basis of only one variable, but the LH surge is unlikely to occur before either the follicle diameter has reached 15 mm and/or the serum E2 level has reached 600 pmol/L.

Results were collected from 11 studies comparing intrauterine insemination (IUI) with intracervical insemination (ICI) of frozen donor semen, 10 studies comparing IUI with timed natural intercourse (NI) or ICI in couples with semen defects and seven studies comparing ICI with NI or ICI in couples with unexplained infertility. IUI significantly increased the pregnancy rate relative to favourably timed ICI in donor insemination (DI) with frozen semen both with and without gonadotrophin stimulation of the female partner (odds ratios (95% confidence interval) 1.92 (1.02-3.61) and 2.63 (1.52-4.54) respectively). The benefit of IUI tended to be less when the pregnancy rate for ICI was high and IUI had no benefit with fresh donor semen. Overall IUI was of significant benefit in the male factor couples compared with NI-ICI (odds ratio 2.20 (1.43-3.39) and the advantage appeared to be maintained when comparison was confined to properly timed ICI although the odds ratios were not significantly greater than 1. IUI had no benefit relative to favourably timed NI-ICI for couples with unexplained infertility; an apparent advantage overall was produced by studies where NI was late. None of the studies on male factor used a sperm function test to define male subfertility and three only included couples with good mucus penetration by sperm. The range of semen defects defined was such that many couples would have had a good chance of conceiving naturally given a normal female partner but nevertheless the overall pregnancy rate (4.8%) was considerably less than in the unexplained group (11.6%), suggesting that some sperm dysfunction was present. We conclude that the available evidence suggests that IUI is valuable for DI with cryopreserved semen and for couples with mild to moderately impaired semen quality and postulate that it overcomes failure to fertilize due to impaired mucus penetration and poor survival in the female reproductive tract.

Purpose: The impact of endometriosis and unexplained infertility on follicular function and fertilization of oocytes in cycles totally unperturbed by exogenous gonadotrophins, when compared with controls with tubal damage, were examined., Methods: In natural cycles, without any exogenous gonadotropins, endocrine and ultrasonographic studies of follicular maturation in 18 women with minor endometriosis (41 cycles), 15 women with unexplained infertility (31 cycles), and 34 women with tubal damage (88 cycles) were performed., Results: The endometriosis group had a significantly longer follicular phase (median: 15, 13, and 13 days). Both endometriosis and unexplained infertility had significantly reduced LH concentrations in follicular fluid compared with tubal damage (median: 12.1, 11.5, and 15.9 IU/L, respectively). Endometriosis was associated with a significantly reduced fertilization rate compared with unexplained infertility or tubal damage (46, 65, and 69%, respectively)., Conclusions: These data show continuing evidence of ovulatory dysfunction leading to reduced fertilization rates in women with minor endometriosis.

A pilot study was designed to examine whether the outcome of embryo transfer in women with a hydrosalpinx might be improved by surgical drainage of the hydrosalpinx at the time of oocyte collection for in-vitro fertilization treatment. A comparative, controlled but retrospective analysis of the results was performed of all women with infective tubal damage aged <40 years old, who had ovulatory cycles, a normal uterus and a partner with normal spermatozoa. A standardized treatment regimen was used. A maximum of three embryos were transferred. Hydrosalpinx was defined by prior hysterosalpingography and/or laparoscopy with transcervical dye injection. A total of 237 embryo transfer cycles in women with hydrosalpinges (tubal distension not visible in 151, visible but not drained in 30 and drained in 56) were compared with 705 embryo transfer cycles in women with tubal disease but no hydrosalpinx. Results were analysed in the first three cycles but also separately in the first cycle to check for bias. Success rates were higher in the first cycle, but did not significantly influence overall differences. Implantation rates were significantly reduced overall in the hydrosalpinx group (8.0 versus 13.2% for controls; P < 0.001), being 8.3% (P < 0.01) in the subgroup without evident tubal distension and 7.5% (not significant) in the drained hydrosalpinx group. This study shows that tubal damage with distal occlusion is associated with a marked reduction in embryo implantation, even in the absence of obvious fluid distension. Surgical drainage of distended hydrosalpinges appears to offer no benefit.

Purpose: Impaired outcome of in vitro fertilization treatment has been related to abnormal luteining hormone (LH) secretion and to the occurrence of a premature LH surge. The purpose of this study was to compare LH serum concentrations, measured by bioassay (LH-b) and immunoassay (LH-i), during early and late follicular phases in normal-ovulatory women who were stimulated with clomiphene, human menopausal gonadotropin (HMG), and human chorionic gonadotropin (hCG), while undergoing in vitro fertilization (IVF) treatment for infertility, due mainly to tubal damage., Results: Of 22 patients, 15 had an LH surge (surge group) before receiving hCG and 7 did not (nonsurge group). LH-b and LH-i concentrations were higher in the late follicular phase than before clomiphene treatment, but the LH-b/LH-i (B/I) ratios remained unchanged and there were no significant differences between the LH surge and the nonsurge groups. In the surge group, the B/I ratio appeared to fall during the LH surge [presurge values, 5.4 +/- 0.5 (SD) and 5.2 +/- 0.5; surge values, 4.9 +/- 0.6 and later 4.0 +/- 0.6], but the differences were not significant, and in some individuals, the B/I ratio later rose as the LH surge progressed., Conclusions: Our findings suggest that interference with IVF outcome by a spontaneous LH surge is due to quantitative and/or exposure time effects on the oocyte, rather than to any qualitative variation in bioactivity of LH.

Mandated managed care of infertility, as for other branches of medicine, demands cost-effectiveness, appropriate use of proven clinical methods, and audit of the services provided. Proper standards, and protocols of clinical diagnosis and selection of treatment need to be agreed, although allowing for valid alternatives. A diagnostic process and classification staged for primary, secondary, and tertiary care as appropriate, which has been derived by consensus, is offered in this paper. It is assumed that all couples would be allowed access to diagnostic services. A national estimate has attributed one-quarter of the costs of full infertility services to diagnostic procedures and three-quarters to treatments. It is assumed that any constraints owing to funding would apply only to access to treatment. One model proposed would limit treatment to those couples and methods which could achieve a 50% birthrate target within a reasonable time limit or number of cycles. Although there is as yet no existing model of managed care on which to base exact costing, it should be possible by initial over-restrictiveness to leave room for annual adjustments of treatment provision and to allow for new developments. Other more equitable ways of sharing resources can be argued, and ethical standards should be agreed in any system of managed care for a population.

A series of 183 patients with positive indirect immunobead tests on semen was studied to determine the correlation in semen between specific antibody types, binding sites, antibody concentration, and fertilizing ability. IgM was present in only 44 ejaculates and was present in sufficient quantity to cause significant binding to immunobeads (i.e. >20% of motile donor spermatozoa) in only three of them. There was no correlation between the percentages of motile donor spermatozoa that bound IgA and IgG immunobeads but the two classes of beads generally bound to the same region of the spermatozoa. A total of 63 couples went on to attempt in-vitro fertilization (IVF) treatment, all with mature eggs recovered. Of these mature eggs, 44% were fertilized and cleaved normally in comparison to 68% in a group of patients with tubal disease. Fertilization rates in individuals followed a bimodal distribution with a substantial number of couples experiencing zero or very poor rates (0-20%), the mode for the remainder lying between 60 and 80%. The fertilization rate tended to decrease as the amount of antibody increased. The percentage of donor spermatozoa that bound to immunobeads, taken as the greater of IgA and IgG, was selected by logistic regression as a significant predictor of poor fertilization (rate <=25%). The predictive power of the equation was improved by including the motile normal sperm concentration but the equation could only account for a small proportion of the total variation in fertilization rate. The presence of antibodies to the sperm head was highly correlated with the antibody concentration but was not selected as a predictor of fertilization. We conclude that the nature of the antigen against which the seminal antisperm antibody is directed may be as important as the antibody concentration in affecting sperm function. There seems to be little practical value in measuring IgM in seminal plasma.

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%, P < 0.01). In samples taking >/=2 days there was increased frequency of significant culture of Gram-negative bacilli (31 versus 12%, P < 0.01) and of overall culture of other potentially pathogenic organisms (26 versus 14%, P < 0.01). 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%), P < 0.05]. 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.

Objective: To determine strictly comparable rates per embryo of implantation and birth of a baby related to the woman's age, which would be representative of natural fertility at least in relative terms., Design: Comparative study of IVF-ET results controlling for confounding variables including cause and duration of infertility, history of previous pregnancy, hormonal treatment, rank cycle of treatment, and numbers of embryos transferred and available., Setting: University comprehensive fertility service., Patients: All couples (n = 561) in their first cycle of treatment reaching oocyte collection, women with normal uterus and ovulatory cycles, and men with normal sperm., Interventions: Standardized methods of pituitary desensitization, ovarian stimulation, and IVF-ET, and maximum of three embryos transferred., Main Outcome Measures: Oocytes, pregnancies, and live births per cycle; fertilization and cleavage rates; embryo implantation and live baby rates., Results: The numbers of oocytes and consequent embryos declined with age but fertilization and cleavage rates rose slightly. Embryo implantation rates were reduced when no more than three embryos were available (9.3 percent), especially in women aged 35 to 39 years (6.2 percent) or older compared with four or more embryos (17.1 percent) but were equally low in all women over 40 years even with more embryos (6.1 percent). In the age bands 25 to 29, 30 to 34, 35 to 39, and 40 to 44 years, the rates per embryo of implantation were 18.2 percent, 16.1 percent, 15.3 percent, and 6.1 percent, respectively, and of a live baby were 15.7 percent, 12.1 percent, 12.0 percent, and 3.5 percent., Conclusions: Embryo implanting ability and survival decline gradually after 30 years of age, but by more than two thirds after 40 years and in younger women with reduced ovarian capacity.

Evidence of pituitary-ovarian dysfunction in unexplained and endometriosis-associated infertility has been reported previously. Hormone-suppressive therapy is often used in an attempt to improve fertility, although benefits have not been proven. Our study examines the effect of progestogen (medroxyprogesterone acetate) treatment on women with endometriosis-associated and unexplained infertility, compared with women with tubal damage as functional controls. Pre-ovulatory follicular size and serum and follicular fluid hormone concentrations were measured, and oocyte collection and in-vitro fertilization were attempted, in natural cycles totally unperturbed by exogenous gonadotrophins, for two cycles before and two cycles following treatment with medroxyprogesterone acetate for 2 months. In the endometriosis and unexplained infertility groups, compared with the tubal group, the treatment led to significant reductions in the integrated luteinizing hormone (LH) values (483 versus 664, 559 versus 762 and 864 versus 820 notional IU/l respectively). There were no changes in serum oestradiol or follicular fluid oestradiol, progesterone, follicle stimulating hormone or LH concentrations after treatment. The results suggest that progestogen therapy has no beneficial effect on the pituitary-ovarian dysfunction which contributes to endometriosis-associated and unexplained infertility.

Objective: To study whether the presence of hydrosalpinx affected success after in vitro fertilisation (IVF) in women with inflammatory tubal damage., Design: Retrospective, nonrandomised study., Setting: University private IVF clinic with complete fertility services., Participants: Two study groups (79 women with hydrosalpinges and 198 women with inflammatory tubal damage but no hydrosalpinx) and a third group (22 sterilised, previously fertile women) for comparison., Main Outcome Measures: Clinical pregnancy and livebirth rates per embryo transfer cycle; implantation and live baby rates per individual embryo transferred., Results: The hydrosalpinx group had a significantly lower implantation rate per embryo (8.2%) and chance of a live baby per embryo transferred (5.6%), compared with the nonhydrosalpinx group (14.9% and 11.2%, respectively). The hydrosalpinx group also had a lower clinical pregnancy rate (23%) and live birth rate per transfer cycle (17%) compared with the nonhydrosalpinx group (30% and 26%), but these differences were not significant., Conclusions: The presence of a hydrosalpinx halves the chance of an embryo implanting, probably due to physical or toxic chemical effects of fluid draining from the hydrosalpinx into the uterine cavity. Women with hydrosalpinges may benefit from distal salpingostomy or salpingectomy as a drainage procedure before in vitro fertilisation treatment, even though such surgery may not increase the chances of natural conception.

Whether stress and infertility are linked as cause or consequence is unclear, and there is no consensus on the most appropriate methods for measuring stress in infertile women. To address this question, we measured changes in biochemical and questionnaire-based assessments of stress in infertile women. Median baseline, follicular phase and pre-operative serum prolactin (229, 311 and 457 mIU/l) cortisol (278, 369 and 496 nmol/l) and state anxiety score (38, 40 and 49) respectively all increased during stimulated in-vitro fertilization (IVF) treatment. There was no such increase in a control group having similar laparoscopic surgery unrelated to infertility, or in women having unstimulated IVF without laparoscopy, suggesting that anxiety levels are greatest in stimulated IVF, increase as a result of the treatment, and are adequately reflected by state anxiety scores. Baseline serum prolactin in unstimulated IVF (384 mIU/l) was significantly higher than control (177 mIU/l), although this was not reflected in serum cortisol or state anxiety score. Trait anxiety was constant within and between groups, suggesting that stress is not contributing greatly to the infertility. Women who achieved a pregnancy had similar state anxiety scores to those who failed, suggesting that the degree of anxiety observed during IVF treatment is unlikely to influence the chance of pregnancy. There was a trend towards lower trait anxiety in women who became pregnant, but the numbers were small.

A prospective controlled study of donor insemination without sperm preparation or ovarian stimulation was performed to compare the use of a cervical cap incorporating an intracervical reservoir with a standard intracervical injection technique to inseminate 0.5 ml cryopreserved semen. Treatments were alternated in successive cycles in each patient after initial randomized selection. A total of 198 patients had 635 treatment cycles (median 3, range 1-7), 309 with reservoir and 326 by standard injection. A total of 56 women became pregnant, 24 (7.8% per cycle) with the reservoir and 32 (9.8% per cycle) by injection. There were no significant differences between the pregnancy rates per cycle overall or cycle-specific cumulative rates calculated using the life-table method. There were no significant differences in age, parity, baseline gonadotrophin measurements, mid-luteal serum progesterone concentrations, frequency of adverse fertility factors in the woman or her partner's cause of infertility between women who conceived and those who failed to conceive. We conclude that use of a cervical reservoir and cap for donor insemination does not offer any advantage over standard intracervical insemination.

To examine the cause of altered follicular fluid steroid levels and lower in vitro fertilization rate observed in infertile women with minor endometriosis, we have compared the production of estradiol (aromatase activity) and progesterone of freshly isolated granulosa cells (3h. incubation) from such women and a control group with tubal or unexplained infertility, having IVF during unstimulated or gonadotropin-stimulated cycles. As previously observed, mature oocytes from women with endometriosis had a reduced fertilization and cleavage rate in vitro in unstimulated cycles (19/37[51%] vs. 69/94[73%], p < 0.05) and stimulated cycles (20/37[57%] vs. 32/39[82%], p < 0.01). Median [95%CI] basal aromatase activity was lower in endometriosis compared with control in unstimulated cycles (2.84[2.03-3.49] pmol E2/10(3) cells/3h, n = 31 vs. 3.63[2.72-3.49], n = 55, p = 0.057) and stimulated cycles (0.31[0.16-0.50], n = 14 vs. 0.99[0.70-1.52], n = 20, p < 0.001). Progesterone production followed a similar pattern in unstimulated (0.56[0.50-0.89] pmol/10(3) cells/3h, n = 29 vs. 1.23[0.69-1.54], n = 52,) and stimulated (0.37[0.20-0.73], n = 16 vs. 0.95[0.72-1.17], n = 21) cycles (p < 0.05). Addition of FSH, LH or hCG (30ng/mL) to the incubation medium enhanced progesterone production 2 to 3-fold, but had no effect on aromatase activity. Our results indicate a defect in granulosa cell steroidogenesis associated with endometriosis, which could affect oocyte function and explain the reduction in fertilizing capacity and subsequent competence of the corpus luteum, and the associated subfertility.

This study examines circulating and follicular hormone concentrations and fertilization of oocytes in cycles totally unperturbed by exogenous gonadotrophins in 10 women (25 cycles) with untreated minimal-mild endometriosis and nine women (23 cycles) with prolonged unexplained infertility compared with 16 women (50 cycles) with tubal damage as functional controls. Endometriosis was associated with a significantly longer follicular phase (median 15, 12, 13 days respectively) and reduced oestrogen secretion (median index area under the curve 3063, 3842, 3805 units respectively) compared with controls. Both endometriosis and unexplained infertility had significantly reduced serum luteinizing hormone (LH) surges [median peak serum (LH) 43, 39, 55 IU/l respectively and median area under the curve 661, 687, 823 units respectively] and reduced LH concentrations in follicular fluid (median 19.6, 10.6, 9.2 IU/l respectively). These findings suggest that infertility associated with minor endometriosis and of apparently unexplained aetiology share a common pathophysiology in impaired LH surge secretion. Whether that represents a primary pituitary disorder or is secondary to a defective ovarian signal is discussed.

Transforming growth factor alpha (TGF alpha) is implicated as a paracrine growth factor in the regulation of human granulosa cell function. To investigate this further, we have examined the actions of TGF alpha on the basal and follicle-stimulating hormone (FSH)-stimulated aromatase activity of human granulosa cells to determine how this growth factor influences oestrogen biosynthesis in the follicle. Granulosa cells from women having in-vitro fertilization during untreated or gonadotrophin-stimulated cycles were cultured for 1-6 days in the presence or absence of FSH or TGF alpha at a range of doses. Aromatase activity, expressed as oestradiol production, was determined after culture during a 3 h test period. After 2 days, TGF alpha (1-300 ng/ml) decreased basal and FSH-stimulated aromatase activity in a dose-dependent manner (ED50 = 3 ng/ml). In contrast, after 4 days, TGF alpha enhanced both basal and FSH-stimulated aromatase activity. Repeated experiments revealed a consistent pattern of inhibition on day 2, which was more marked in the presence of FSH (reduction by 30.6 +/- 9.1%, mean +/- SEM; n = 14; P < 0.01), and stimulation on day 4 in both the absence (increased by 61.4 +/- 20.6%, mean +/- SEM; n = 6; P < 0.05) and presence of FSH (increased by 36.0 +/- 15.2%, mean +/- SEM; n = 8; P < 0.05). The results provide further evidence that TGF alpha is a paracrine factor in the control of oestrogen biosynthesis, but the actions can be either inhibitory or stimulatory depending on the duration of exposure.

The majority of women with tubal/pelvic infective damage have a poor prognosis for natural conception, and in-vitro fertilization and embryo transfer would be a better primary choice. Other determining factors are sperm disorder or the woman's age, and personal issues may be of overriding importance. The most important requirement in the first place, however, is well defined, comparable statistical information on time-specific cumulative pregnancy rates related to specific diagnostic features. The main aims of this review are to analyze the most useful comparable data available and present them in graphical form for easy reference and clear understanding (by the patients too), and to try to derive a practically simple and prognostically valuable diagnostic classification.

Our objective was to assess the efficacy of in-vitro fertilization (IVF) in natural ovarian cycles in couples with tubal and unexplained infertility. A prospective study design was used. A total of 39 fully investigated couples, who were patients at the Reproductive Medicine Unit, St Michael's Hospital, Bristol, UK, took part; they were diagnosed with either tubal disease (n = 26) or unexplained infertility (n = 13). Procedures involved daily capillary blood sampling, daily vaginal ultrasonography and vaginal oocyte recovery under sedation at mid-cycle. The main outcome measures were fertilization, implantation and pregnancy rates. Although more of the women with tubal disease were parous, there were no other significant differences between the two groups. The 39 couples with infertility of tubal or unexplained aetiology had 79 cycles of IVF in otherwise completely natural cycles. The overall fertilization rate was 80% and the implantation rate was 14.0%. A trend was observed for higher success rates in women with tubal disease. We conclude that natural cycle IVF and embryo transfer offers an acceptable chance of pregnancy and an opportunity for the in-depth investigation of follicular and ovarian function in couples with defined causes of infertility. The possibly lower success rate in women with unexplained infertility warrants further study of follicular function and endocrinology.

The treatment of infertility due to severe oligoasthenoteratozoospermia has been revolutionized by the introduction of the technique of intracytoplasmic sperm injection. However, techniques which involve injection into the oocyte of polyvinylpyrrolidone solution as a vehicle for the selected spermatozoon have caused concern since the possible harmful effects of polyvinylpyrrolidone have not been fully investigated. This study was performed to investigate the potential mutagenic effect of polyvinylpyrrolidone on cultured human somatic cells, at the concentration used for intracytoplasmic sperm injection, in addition to a possible alternative vehicle, methyl cellulose, using the technique of sister chromatid exchange analysis. The results showed no increase in the basal frequency of sister chromatid exchanges with polyvinylpyrrolidone (median 5.0, 95% interval 5.00-6.00) or with methyl cellulose (median 6.0, 95% interval 4.22-6.00) in comparison with the negative control (saline: median 6.0, 95% interval 5.00-7.00), and in contrast to the positive control (mitomycin C: median 25.0, 95% interval 22.23-28.77). This finding suggests that polyvinylpyrrolidone and methyl cellulose do not cause DNA lesions resulting in sister chromatid exchanges, and provides reassuring evidence concerning their use in sperm injection procedures.

The results are reported of 2,204 cycles of treatment started for in vitro fertilisation and embryo transfer or gamete intrafallopian transfer, during 5 years, 1990-1994, using only follicle-stimulating hormone (FSH) preparations to stimulate the ovaries following pituitary desensitisation, combined with greatly simplified scheduling and monitoring of treatment. The physiological principles underlying these choices are discussed. In all women under 40 years of age and men with normal sperm, the use of unpurified urinary FSH in 1990-1993 resulted in oocyte collection in 94% of cycles started, pregnancy in 29% and live births in 23%. Using highly purified urinary FSH (uFSH-HP; Metrodin HP) during 1994, the rate for oocyte collection was 97% and pregnancy 25% (birth rates not yet available). The difference compared with previous years was not significant. A study of 93 first cycles using uFSH-HP showed that the dosage required was usually (expressed as medians) 24 ampoules over 12 days (2 ampoules/day) resulting in 9 oocytes (range 2-36) of which 93% were mature and 64% resulted in cleaving embryos. The results are comparable with the best using human menopausal gonadotropin or unpurified FSH and classical detailed monitoring.

Rat pituitary monolayer bioassays were used to compare gonadotrophin surge-attenuating factor (GnSAF) bioactivity in follicular fluid from 12 follicles in 10 spontaneously cycling women with that in pooled follicular fluid from women undergoing ovulation induction. Expressed as ED50S (microliter follicular fluid/well producing 50% of maximal effect), GnSAF bioactivity was detectable in all spontaneous follicular fluid samples (1.4-33.3 microliters/well) and in follicular fluid from women undergoing ovulation induction (6.8 microliters/well). This GnSAF bioactivity was unaffected by pre-incubation with an inhibin antibody. When the data were grouped according to whether the recovered oocytes fertilized in vitro or not, the fertilized group contained significantly greater GnSAF bioactivity than the unfertilized group (5.3 +/- 1.1 and 14.1 +/- 2.6 microliters/well respectively, P < 0.05). While both inhibin bioactivity (9.7 +/- 1.4 and 28.9 +/- 12.1 microliters/well) and immunoreactivity (36.8 +/- 2.2 and 21.0 +/- 3.0 and ng/ml) were also greater (P < 0.01) in the fertilized compared with the unfertilized groups respectively, there were no other significant differences between the two groups. We conclude that GnSAF is found in follicular fluid from spontaneously cycling women, supporting in-vivo evidence for the involvement of GnSAF in feedback control of the ovary-pituitary axis.

The relative prognosis for further assisted conception treatment (without micro-injection) after initial unexpected failure of fertilization in apparently favourable couples undergoing in-vitro fertilization (IVF) treatment was assessed. After their first cycle of treatment, 481 consecutive couples were grouped according to their fertilization (including cleavage) rate per oocyte into five bands. Proportions of couples proceeding to further cycles of treatment by IVF or gamete intra-Fallopian transfer (GIFT) and resulting fertilization and pregnancy rates were compared. Pregnancy rates in the first cycle of treatment were significantly related to fertilization rate. The fertilization rate was zero in 13 couples (3%) and only 1-24% in 18 (4%). There were no significant differences between these groups in the proportions proceeding to further treatment (31, 50%) compared with others (overall 37%, including some treated by GIFT), or in their median fertilization rates (75, 60% compared with 67%--IVF cycles only), pregnancy rates (20, 38% of cycles compared with 37%--IVF or GIFT) or birth rates (20, 38% of cycles compared with 31%--IVF or GIFT). Amongst couples whose initial fertilization rate was > or = 50% there was no fertilization in 4% of subsequent IVF cycles. We conclude that in couples with well defined favourable conditions, including tests of sperm function for assisted conception treatment, who have unexpected failure of fertilization, the prognosis for further treatment remains favourable without resort to more complex investigations or micro-injection methods. Such failure occurs infrequently and generally as a random event, and should have no appreciable effect on life-table calculation of cumulative pregnancy and birth rates in this group of patients.

Objective: To determine the relative value of the woman's age, basal follicle stimulating hormone (FSH), basal luteinising hormone (LH) and menstrual cycle pattern (all defined prior to treatment) in predicting the ovarian response to gonadotrophin stimulation for in vitro fertilisation., Design: Open, descriptive cohort study., Patients: One hundred and seventy-one consecutive ovulatory women undergoing their first cycle of in vitro fertilisation with ovarian stimulation after pituitary desensitisation., Interventions: Measurement of basal (early follicular phase) and down-regulated concentrations of serum FSH and LH, and calculation of age at treatment and of median length of menstrual cycles and range of variation prior to treatment., Main Outcome Measures: Duration and amount of gonadotrophin stimulation to achieve follicular maturity, number of mature follicles, peak serum oestradiol concentration and number of mature oocytes, were compared between banded values of variables studied., Results: Increasing basal FSH concentrations were significantly associated with reducing oestradiol levels, numbers of mature follicles and oocyte yield even when the FSH levels were still within the normal range though above average (6 to 8.9 i.u./l). There were similar but weaker associations with FSH levels after down-regulation. There were also significant differences between women over and under 40 years old in their oestradiol levels, numbers of follicles and of oocytes. Analysis of variance showed significant independent association of basal FSH with both oestradiol and numbers of oocytes, but not of age, menstrual pattern, or serum LH concentrations., Conclusion: Serum FSH is more sensitive than the woman's age in determining her ovarian responsiveness to stimulation. LH concentrations and menstrual cycle patterns are unhelpful.

It has been suggested that seasonal variation in endometrial receptivity may occur in women, which could affect the likely success of in-vitro fertilization (IVF) treatment. We therefore studied implantation rates (fetal sacs as a proportion of embryos transferred) as an indirect index of receptivity in a narrowly defined population of women under 40 years old with normal ovulatory cycles and normal uterus and men with normal sperm function. A total of 577 cycles of IVF treatment were undertaken using a standard protocol of pituitary desensitization and ovarian stimulation during the 3 years 1990-1992. Results were compared between calendar months and 3-month seasons. The overall implantation rate was 14.9% of embryos, and the clinical pregnancy rate was 30.3% of cycles reaching egg collection. There were no significant differences in the monthly rates of eggs collected, fertilization and cleavage, or embryos transferred. Implantation rates varied to a greater extent but analysis of variance showed no seasonal variation. These findings do not support a seasonal variation in ovarian responsiveness or endometrial receptivity when stimulated for IVF treatment, but larger studies are needed for firm conclusions to be drawn.

Objective: Analyse outcome of FSH therapy alone after pituitary desensitization for assisted conception to compare with published results of conventional hMG., Design: Descriptive study of complete series of patients undergoing IVF-ET or GIFT treatment using the chosen drug protocol without exception., Setting: University private IVF-ET clinic within a comprehensive fertility service., Patients: All couples (n = 773), including 10% > or = 40 years old, treated by IVF-ET or GIFT (1,097 cycles started and 1,012 attempted egg recoveries) for mainly tubal pelvic infective damage (36% of cycles), endometriosis (16%), sperm disorders (14%) and prolonged unexplained infertility (34%) during 3 calendar years, 1990 to 1992., Interventions: Ovarian stimulation using FSH alone (urofollitropin, Metrodin; Serono Laboratories Limited, Welwyn Garden City, United Kingdom) after pituitary desensitization using buserelin acetate nasal spray (Suprefact; Hoechst, Hounslow, United Kingdom) from the previous midluteal phase, monitored by ultrasonography and serum E2 measurements, followed by standard IVF-ET or GIFT treatment methods limited to the transfer of no more than three embryos or eggs., Outcome Measures: Rates per cycle started of cancellation of egg recovery, failure of egg recovery, clinical pregnancy (ultrasound detection of sac), livebirths, and cumulative pregnancy rates (PR) and birth rates., Results: In women < 40 years old and men with favorable sperm (77% of couples and 84% of cycles) the cycle cancellation rate of egg recovery was 7%; attempted egg recovery was successful in every case. For IVF-ET the clinical PR per started cycle and the livebirth rate were 27% and 23%, respectively, and for GIFT 39% and 33%, respectively. The four-cycle cumulative PR by either treatment was 77% and livebirth rate 68%. In women > 40 years old, the cycle PR and birth rate were 14% and 8%, respectively. In cases of sperm disorder the rates in women < 40 years old were 17% and 14%, respectively, and > 40 years old were 18% and 0, respectively., Conclusions: By comparison with the best worldwide results of assisted conception employing pituitary desensitization, the findings demonstrate that FSH alone to stimulate the ovaries is fully effective and highly successful, and supplementation with LH is not needed.