The efficacy of synthetic adhesion barriers in infertility surgery.
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Biomedical subjects
Publications and source records attributed to I D Cooke.
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OBJECTIVE: To determine whether Interceed, an absorbable adhesion barrier, confers any additional benefit over conventional microsurgery, including the use of an adjuvant (hydrocortisone), in the prevention of adhesion reformation after pelvic microsurgery. DESIGN: A prospective, randomised, controlled study. SETTING: Jessop Hospital for Women, Sheffield, UK. SUBJECTS: Twenty-eight women who underwent pelvic microsurgery for infertility or for chronic pelvic pain and who had bilateral pelvic adhesions and deperitonealised areas following adhesiolysis. INTERVENTIONS: Following microsurgical adhesiolysis, one side of the pelvis was randomised to have its deperitonealised areas covered with Interceed, whereas the contralateral side served as the control. A second look laparoscopy was carried out 3 to 14 weeks after microsurgery to evaluate adhesion reformation. MAIN OUTCOME MEASURE: The amount of adhesion reformation at second look laparoscopy compared with the amount of deperitonealised area exposed following microsurgical adhesiolysis. RESULTS: The use of Interceed resulted in a significant reduction of adhesion reformation over and above that achieved by conventional microsurgical techniques with hydrocortisone as an adjuvant. CONCLUSION: Interceed, an absorbable adhesion barrier, is of value in the prevention of adhesion reformation and may be used in conjunction with hydrocortisone instilled intraperitoneally at the conclusion of microsurgery.
Natural cycle IVF (NIVF) arose from a wish to understand intrafollicular events in couples with unexplained infertility. Single follicle aspiration required unusual technical skill and a precise understanding of the endocrinology in the ostensibly normal cycle. The application of NIVF to all candidates for assisted conception resulted in a low delivery rate. However once data had accumulated it became apparent that age, follicular phase FSH concentrations and other endocrine abnormalities were associated with high failure rates. The concept of using NIVF as a preliminary screening cycle arose. By early elimination of some candidates and selective inclusion of others a highly cost effective regime can be developed. Taking delivery rates into account the cost per maternity is only half that of stimulated IVF. Using clear cut algorithms for the investigation of different categories of infertility the place of NIVF can be defined. Current UK discussions relate to exclusions from access to IVF. Biological exclusions such as age could further enhance the cost effectiveness of NIVF. When NIVF can contribute to at least 50% of cycles in an assisted conception programme it has the potential to have a major economic impact.
From 1944 when the first British Report on a National Maternity Service was published until 1989 there have been seven publications on the Maternity Services. Against this background the Shearman Report is described in comparison with its British counterparts. There has however been much debate in the UK since 1989 with a redesign of the National Health Service. A sub committee of the House of Commons (Winterton) advocated major changes in maternity services and the Government responded with a detailed critique announcing the appointment of an Expert Maternity Group (Cumberlege) which has just published its recommendations for widespread consultation. The three Royal Colleges have published a joint report and in the next year Government policy will be published. Scotland however has developed an independent view and has progressed further an analysis and rational planning. The fate of the Shearman report will be awaited with interest.
The effects of treatment with danazol (600 mg daily) on haemostatic and haematological function were investigated in 18 pre-menopausal women with endometriosis. Blood samples were taken at 2 pre-treatment visits, at 6, 12 and 24 weeks on treatment, and at 6 weeks after discontinuation of the drug. Haemoglobin, red cell count, haematocrit and platelet count all rose significantly during treatment with danazol (p < 0.01 vs. baseline). Plasma fibrinogen levels fell significantly (p < 0.01), while whole blood viscosity increased during treatment and remained significantly elevated at follow-up. The prothrombin time shortened, but remained within normal limits, and there were no significant changes in factor VII:C, VIIa, or fibrinopeptide A. No significant changes were found in platelet function. Plasma B-beta 15-42 increased significantly. Functional levels of protein C, protein S, and antithrombin III, all rose significantly, above the normal range, while C4b-binding protein levels fell. We conclude that the observed changes in coagulation inhibitors and fibrinolytic activity may be considered beneficial in the context of venous thromboembolism. The rheological effects, however, indicate a degree of caution in the use of the drug in individuals considered to be at risk from arterial cardiovascular disease.
OBJECTIVE: To correlate the severity and extent of pelvic adhesions, as noted at laparotomy for microsurgery, with the presence and extent of fallopian tube intraluminal pathology, as noted using salpingoscopy. DESIGN: Prospective clinical study. SETTING: A university teaching hospital. PATIENTS: Twenty patients presenting for pelvic microsurgery between July 1992 and January 1993. INTERVENTIONS: Salpingoscopy was performed at the time of microsurgery and intraluminal pathology was scored. An objective assessment of the extent of pelvic adhesions was made using standardized adhesion score systems. RESULTS: There was a strong correlation between the degree of intratubal damage and the extent of pelvic adhesions when the etiology was previous pelvic inflammatory disease (PID) but not when the underlying etiology was endometriosis. However, in the endometriosis subgroup, intraluminal ampullary pathology was noted in 27% of tubes assessed, and intraluminal fimbrial pathology was noted in 36% of tubes assessed. Intraluminal tubal pathology also was noted in a number of cases where the underlying etiology was previous surgery for benign disease. CONCLUSIONS: This study confirms previous reports that, in cases of PID leading to adhesions, there is a high incidence of intraluminal pathology. However, this study also demonstrates that intraluminal pathology is often associated with adhesions arising from other etiologic groups, suggesting that intraluminal assessment is required for all patients in whom adhesiolysis for fertility is considered.
OBJECTIVE: To compare the effect of human oviductal fluid on sperm motility and hyperactivation during 9 hours' incubation in vitro with follicular fluid (FF) and medium controls. DESIGN: Fertile donor spermatozoa were allowed to penetrate human cervical mucus in vitro and then recovered and incubated in either 30% human oviductal fluid, 20% FF, or medium for up to 9 hours. Sperm motion characteristics were measured using a sperm motility analyzer. SETTING: The donor insemination program at the University Clinic within the Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: All donors used in this study were involved in the donor insemination program. MAIN OUTCOME MEASURES: Sperm motility, hyperactivation, curvilinear velocity, progressive, lateral head displacement, and linearity were measured using a sperm motility analyzer. RESULTS: After 9 hours' incubation, spermatozoa in human oviductal fluid had a significantly higher percentage motility than sperm incubated in FF or the control medium. A more linear sperm motion was consistently observed in the spermatozoa incubated in human oviductal fluid: significantly different from FF and media at 3 hours and 6 hours. The effect of human oviductal fluid on maintaining sperm motility was not affected by the addition of P. CONCLUSION: Human oviductal fluid can maintain sperm motility in a mechanism that is not mediated by the low concentration of P. We suggest that human oviductal fluid is a favorable environment for sperm survival.
OBJECTIVE: To determine the effects of clomiphene citrate (CC) and cyclofenil on cervical mucus (CM) volume and receptivity sampled serially over the periovulatory period. DESIGN: Using prospective luteinizing hormone (LH) timing CM volume and receptivity were compared in standard CC and cyclofenil-stimulated cycles using normal ovulatory cycles as controls. LOCATION: The Donor Insemination Unit at the University Research Clinic, Sheffield, United Kingdom. PATIENTS: Twenty anovulatory patients and 10 normally ovulating patients, all of whom were participating in a treatment cycle of donor insemination. INTERVENTIONS: The 20 anovulatory patients were allocated at random into two groups: group 1 was administered 50 mg of CC on days 2 to 6 of the menstrual cycle; group 2 was administered 400 mg of cyclofenil on days 3 to 12 of the menstrual cycle. All the patients were given a single treatment of donor insemination 24 to 36 hours after the onset of the LH surge. RESULTS: Clomiphene citrate and cyclofenil were shown to exert differential impacts on CM quantity and quality. In terms of quantity, the CC patients produced significantly lower volumes of CM than the cyclofenil patients and controls. In terms of quality, the CC patients and controls produced CM of similar receptivity, whereas the cyclofenil patients produced CM that was significantly more receptive to sperm than both the CC patients and controls. CONCLUSIONS: Neither CC nor cyclofenil exerted a detrimental impact on CM quality throughout the periovulatory period.
OBJECTIVE: To determine the effects of leukocytes in semen on sperm quality and the ability to achieve conception. DESIGN: A prospective analysis of 512 couples attending a regional infertility clinic. Leukocyte subsets were quantified using a monoclonal antibody-based staining procedure. In addition to basic seminal parameters (density, motility, morphology, and antisperm antibodies), reactive oxygen species and immature germ cells were also quantified in the semen of each patient. The presence or absence of a treatment-independent conception was determined 22 months after the start of the study. Semen parameters were then related to the ability to conceive. SETTING: University-based center for reproductive medicine. PARTICIPANTS: Success or failure to conceive was recorded from 512 couples. Couples were then selected to minimize the influence of any pathology of the female on outcome. A final study group of 229 couples, in which the women had regular menstrual cycles, ovulatory midluteal serum P levels of > 18 nmol/L, and patent fallopian tubes was finally selected for analysis. MAIN OUTCOME MEASURE: Pregnancy. RESULTS: Leukocyte concentration (total or individual subsets) was not associated with either reduced semen quality or conception rates. Similarly, neither reactive oxygen species or antisperm antibody (immunobead) concentration had any bearing on the outcome. Of all semen parameters measured, only the level of immature germ cells was found to be negatively associated with the rate of conception. CONCLUSION: Measurement of seminal leukocytes in routine semen analysis appears to be of little prognostic value with regard to male fertilizing potential. As reactive oxygen species and antisperm measurement were of similar predictive value, the term "immunologic male infertility" should be redefined.
A prospective study was performed to determine whether a relationship exists between infertility as a result of pelvic adhesions, and raised follicle stimulating hormone (FSH). A total of 66 patients, who had a diagnostic laparoscopy and dye performed as part of their infertility work-up, had an early cycle serum FSH drawn one to two cycles after this procedure. Patients were divided into two groups, one with pelvic adhesions as a result of surgery, infection or endometriosis, and a control group consisting of those with a normal pelvis at laparoscopy or with minimal/mild endometriosis without adhesions. In the adhesion group, a correlation was noted between American Fertility Society (AFS) adhesion score and basal FSH concentration, although all FSH values for this group were within the normal range. This study suggests a correlation between pelvic adhesions and ovarian compromise, but a larger study involving more severe cases of adhesions is required to determine whether this finding is of clinical importance.
This study aimed to determine the number and distribution of spermatozoa within the human Fallopian tubes around ovulation. Parous women, undergoing total abdominal hysterectomy for menorrhagia, were inseminated with either partner's semen (3/10) or donor semen (7/10). Approximately 18 h later both Fallopian tubes were ligatured into ampullary, isthmic and intramural regions. These were removed and assessed for sperm content by flushing, scanning electron microscopy (SEM) or homogenization. A median of 251 spermatozoa were recovered (range, 79-1386). The number of spermatozoa within each tube was not significantly different. The ovulatory ampulla contained a significantly (P < or = 0.01) larger percentage of spermatozoa than the non-ovulatory ampulla. The number of motile spermatozoa inseminated was not significantly correlated to the number of spermatozoa recovered, but a trend was identified. The time between the onset of the luteinizing hormone surge and hysterectomy was significantly correlated (P < or = 0.01) to the number of spermatozoa within the intramural regions, but not to the tubal sperm distribution. Spermatozoa were not observed, by SEM, bound to the tubal epithelium. These data suggest that, after artificial insemination at least, sperm access to the human Fallopian tube may be controlled, but that ovulation does not affect the redistribution of spermatozoa between tubal regions and that the isthmus does not appear to act specifically as a sperm reservoir.
To examine the value of the measurement of oestradiol/progesterone ratios in the peri-implantation period, three different types of cycle were studied; natural cycles (n = 13), cycles treated with anti-oestrogens (n = 19), and artificial cycles (n = 41) produced by six different hormone replacement regimens. Normal endometrial development was found to occur across a wide range of oestradiol/progesterone ratios. There was no significant correlation between the oestradiol/progesterone ratios and results of endometrial dating. The results suggest that oestradiol/progesterone ratios are of limited value in predicting endometrial development at the time of implantation.
In the present study attempts have been made to express in quantitative terms the fine structure of the endometrial glandular epithelium in well-timed biopsies from fertile women during the early luteal phase. Biopsies from women with unexplained infertility have also been examined. Certain abnormalities of glandular maturation were found in these women. The nuclear channel system was not present at day luteinizing hormone (LH) + 4 in the infertile group while at LH + 6 there were more cells containing this feature than seen in the fertile group. There also seem to be abnormalities associated with intracellular deposits of glycogen-rich material and mitochondrial elaboration in the infertile women. Changes in the secretory apparatus and rough endoplasmic reticulum were observed. The evidence from the present study suggests that the endometria in the examined group of infertile women is responsive to steroidal stimulation. This response however, may be delayed or inadequate.
The process of sperm transport from the cervix, where a leukocytic reaction is initiated, through the uterus to gain access to the site of fertilization is very poorly understood. This preliminary study was designed to utilize a uterine flushing technique to determine firstly, the number of spermatozoa that can be recovered from the uterine cavity at 4 h post-insemination, around the time of ovulation, and secondly, to establish whether the spermatozoa initiate a leukocytic response while present. Uterine flushing was carried out in 10 potentially fertile women at 4 h post-insemination with donor semen, 24-36 h after the onset of the luteinizing hormone (LH) surge. The flush fluid was analysed for the numbers of spermatozoa and leukocytes present. In 8/10 women spermatozoa were retrieved from the uterus, in consistently low numbers (median 46, range 3-415). In 5/5 women leukocytes were recovered (median, 2.75 x 10(8)/l, range 2.0 x 10(8)-12.7 x 10(8)/l) from an origin other than peripheral blood contamination. These results suggest firstly that the flushing technique was a consistent method for retrieving spermatozoa and leukocytes from the uterine cavity, secondly that only low numbers of spermatozoa can be retrieved on flushing and thirdly that the leukocytic reaction to spermatozoa extends to the uterine cavity.
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A retrospective study was designed to examine the relationship between luteinizing hormone (LH) concentrations in the follicular phase and endometrial development in the luteal phase of natural and artificial cycles. Two types of cycle were studied: natural cycles (n = 51) in subjects with unexplained infertility were divided into two subgroups, depending on whether LH measurements in the late follicular phase were based on urine (n = 24) or plasma (n = 27) samples; and artificial cycles (n = 17), produced by the administration of a standard hormone replacement therapy, in two subgroups of women, those with premature ovarian failure (n = 10) in whom plasma LH concentrations were high, and those with unexplained infertility (n = 7) who had their hypothalamic pituitary-ovarian axis down-regulated and in whom plasma LH concentrations were low. The correlation between plasma or urine concentrations of LH in the follicular phase and the results of endometrial biopsy obtained in the luteal phase was calculated. In natural cycles, LH concentrations were similar in those with normal or retarded endometrium, and there was no significant correlation between high LH concentration and retarded endometrial development. In artificial cycles, endometrial development was not different between those with low LH concentrations (down-regulated by Zoladex) and those with high LH concentrations (premature ovarian failure). Endometrial development in the peri-implantation period does not appear to be influenced by LH concentration in the follicular phase. The reported association between high LH concentration and poor reproductive performance cannot therefore be explained by abnormal implantation consequent upon retarded endometrial development.
In order to investigate whether the endometrium of women with unexplained infertility differs immunologically from the endometrium of normal fertile women, a panel of six monoclonal antibodies was used to characterize the presence of the beta 1-integrins or very-late-activation antigens (VLA) in the different endometrial compartments. Precisely timed endometrial biopsies at 4, 7, 10 and 13 days following the luteinizing hormone surge were obtained from 24 normal fertile women (group I) and 24 women suffering from unexplained infertility (group II). Frozen sections were labelled using an avidin-biotin peroxidase technique. VLA-1, VLA-2 and VLA-3 were present in glandular epithelium, stromal cells and vessels of both groups. VLA-4 was detected in group I but was absent from glandular and surface epithelium of group II. VLA-5 was not present in any of the specimens. VLA-6 was identified primarily in the basement membrane of vessels, glandular and surface epithelium in both patient groups. This study indicates that most beta 1-integrins are present in endometrium throughout the luteal phase of the menstrual cycle. The differences observed between the two groups may contribute to unexplained infertility.
Fertility difficulties, along with their investigation and treatment, are widely believed to cause significant psychological problems. This study was designed to investigate the efficacy of a non-directive counselling intervention with couples undertaking their first cycle of in-vitro fertilization treatment. Couples were randomly assigned to either a control group, given information about the treatment programme, or to an experimental group, given the same information plus three sessions of counselling before, during and on conclusion of the first treatment cycle. Psychological assessments were made at three points in the treatment process. Ratings were also obtained from the couples on the stress engendered by different parts of the treatment, the effects on their relationship and satisfaction with counselling. The results showed the patients to be generally well adjusted and anxiety levels dropped over the course of treatment. Counselling compared to information alone did not lead to any enhanced reduction in levels of anxiety or depression. The implications of the findings for service provision are discussed.