Adhesion-related readmissions following gynaecological laparoscopy or laparotomy in Scotland: an epidemiological study of 24 046 patients.

BACKGROUND: Gynaecological laparotomies are associated with considerable adhesion-related burdens; however, few data are available concerning laparoscopic surgery. This study evaluated the epidemiology of adhesion-related readmissions following open and laparoscopic procedures. METHODS: Records from 24,046 patients undergoing gynaecological surgery in Scottish National Health Service hospitals during 1996 were assessed retrospectively. Cohorts comprised 15,197 patients undergoing laparoscopic surgery and 8849 patients undergoing laparotomies. Adhesion-related readmission episodes (directly and possibly related) were assessed over 4 years following initial surgery and were expressed as percentages of the number of initial procedures. RESULTS: Directly adhesion-related readmissions 1 year after initial laparoscopic surgery were: in the high-risk group (adhesiolysis and cyst drainage) 1.3%; medium-risk (therapeutic and diagnostic procedures not categorized as high- or low-risk) 1.5%; and low-risk (Fallopian tube sterilizations) 0.2%. Readmissions for laparotomy following surgery on the Fallopian tubes were 0.9%, ovaries 2.1%, uterus 0.6% and vagina 0%. Readmissions occurred at reduced rates in the second, third and fourth years after surgery. Exclusion of patients who underwent surgery within the previous 5 years resulted in reduced readmission rates following laparotomy and high-risk laparoscopy. CONCLUSIONS: With the exception of laparoscopic sterilizations, open and laparoscopic gynaecological surgery are associated with comparable risks of adhesion-related readmissions.

Excessive follicular response to controlled ovarian stimulation in a woman with menopausal FSH levels: case report.

A suspected poor responder to controlled ovarian stimulation (COS), with menopausal levels of follicular phase serum FSH, required coasting due to an excessive ovarian response. A 27 year old woman was referred to our Fertility Centre for ovum donation following repeated elevated, early follicular phase FSH levels (34.3, 27.1, 20.3 IU/l). Further investigations revealed the presence of antiovarian antibodies and a trial of COS, with the additional use of prednisolone, was proposed in view of her regular 28 day cycle. As 23 follicles were noted and an oestradiol level of 10,461 pmol/l following 7 days of stimulation with 450 IU of recombinant FSH per day, gonadotrophins were withheld for 9 days. Ten oocytes were retrieved and two grade I embryos were transferred. Pregnancy did not occur and she developed mild ovarian hyperstimulation syndrome. During a second cycle, multiple follicular development was again observed with an oestradiol level >13,200 pmol/l, despite a lower dose of gonadotrophin, and coasting was required for 4 days. Nineteen oocytes were collected, of which nine fertilized and cleaved. Two grade I embryos were replaced, leading to a singleton pregnancy. This patient subsequently had a vaginal delivery of a normal male baby at term. Young women with regular menstrual cycles and grossly elevated FSH levels may benefit from further investigation of autoantibodies and their ovarian response to exogenous gonadotrophins.

Male infertility.

Infertility affects 13-18% of couples and growing evidence from clinical and epidemiological studies suggests an increasing incidence of male reproductive problems. The pathogenesis of male infertility can be reflected by defective spermatogenesis due to pituitary disorders, testicular cancer, germ cell aplasia, varicocele and environmental factors or to defective sperm transport due to congenital abnormalities or immunological and neurogenic factors. Recent studies suggest an increased incidence of genetic disorders related to male infertility which may affect different levels, interfering with germ cell generation and maturation or leading to the production of non-functional spermatozoa. The identification of genetic causes of male infertility raises the issue of the transmission of defects to the offspring, a situation that is becoming more important given the increasing use of intracytoplasmic sperm injection (ICSI), a procedure in which the natural selection of the spermatozoa is by-passed. Fertilization can occur in vitro using ejaculated, epididymal or testicular spermatozoa, either fresh or frozen-thawed, providing opportunities hitherto not possible for men to be genetic fathers.

Clinical evaluation of three different gonadotrophin-releasing hormone analogues in an IVF programme: a prospective study.

The efficacy and safety of short acting buserelin and nafarelin intranasal spray were compared to long acting leuprorelin depot intramuscular or subcutaneous injection in this prospective study of 157 women undergoing controlled ovarian hyperstimulation (COH) for in-vitro fertilisation (IVF). Patients were allocated to three groups to receive buserelin 150 microg nasal spray three times daily (Group B), nafarelin nasal spray 400 microg twice daily (Group N), or leuprorelin depot 3.75 mg once by intramuscular or subcutaneous injection (Group L) for pituitary desensitisation prior to commencing COH with human menopausal gonadotrophins (hMG) according to the Centre's protocol. The mean (+/-S.D.) age (years) (32.6+/-3.8: Group B, 32.1+/-3.3: Group N versus 32.1+/-3.3: Group L); mean (+/-S.D.) total dosage of hMG (ampoules) (37.5+/-16.1: Group B, 39.8+/-14.2: Group N versus 41.9+/-12.6: Group L) and mean daily dosage of hMG (ampoules) (3.1: Group B, 2.8: Group N versus 3.0: Group L) seen were not statistically significantly different. The duration between starting the different gonadotrophin-releasing hormone (GnRHa) and the beginning of the next menstrual period was also not seen to be statistically significantly different between the three groups (Group B: 10+/-5.5, Group N: 9.1+/-4.1 versus Group L: 8.2+/-3, days). The number of abandoned cycles was higher in Group L (17% versus 11.8%: Group B and 11.3%: Group N) but this difference did not reach statistical significance. The clinical pregnancy rates per oocyte retrieval and per embryo transfer procedure were respectively, 31.1, 35% in Group B, 12.8, 14% in Group N versus 20.5, 23.7 in Group L and were not seen to be statistically significantly different even when ongoing pregnancy rates were compared. Apart from a statistically significantly greater incidence of allergic nasal reactions in the nafarelin group (P=0.001), all other side-effects were not shown to be statistically significantly different between the three groups. We conclude that a single dose of leuprorelin depot can be considered to be as an equally effective alternative to multiple doses of buserelin or nafarelin for pituitary desensitisation in women undergoing COH for IVF.

Value of measuring serum FSH in addition to serum estradiol in a coasting programme to prevent severe OHSS.

BACKGROUND: Withholding gonadotrophins (coasting) can reduce the risk of severe ovarian hyperstimulation syndrome (OHSS) in patients having assisted reproduction therapy. This requires daily serum estradiol (E(2)) measurements, which occasionally have been seen to decline suddenly and sharply. METHODS: To increase the sensitivity of the coasting programme we measured serum FSH in parallel with E(2) in patients at risk of developing OHSS. RESULTS: Out of a total of 1240 cycles, 106 were coasted and in 89 both serum E(2) and FSH were measured at least twice during the coasting period. One case of late severe OHSS was encountered in the study group. The serum FSH declined by a rate of 24.3 +/- 4.5% per day. Serum E(2) level reached a 'safe level' of <10,000 pmol/l when the serum FSH declined to 5 IU/l or less. CONCLUSION: The results from this study show that measuring serum E(2) and FSH can assist in predicting the point at which serum E(2) has declined to a level safe enough to administer the trigger HCG.

High concentrations of CA 125 in uterine flushings: influence of cause of infertility and menstrual cycle day.

Uterine flushings were obtained under transvaginal ultrasonographic control from 132 women presenting for investigation and treatment of infertility. Levels of CA 125 were measured by radioimmunoassay and results expressed in relation to the total protein concentration of the same flushings. CA 125 was detected in uterine fluid at levels higher than those previously reported in peripheral blood. Uterine fluid CA 125 concentrations varied throughout the menstrual cycle, being highest in the mid-follicular phase (days 6 to 10). Uterine fluid CA 125 concentrations may reflect endometrial secretion of this protein more directly than serum levels. CA 125 concentrations did not vary according to the cause of infertility but further work in larger numbers of women is required.

Postoperative adhesions: ten-year follow-up of 12,584 patients undergoing lower abdominal surgery.

PURPOSE: Postoperative adhesions are a significant problem after colorectal surgery. However, the basic epidemiology and clinical burden are unknown. The Surgical and Clinical Adhesions Research Study has investigated the scale of the problem in a population of 5 million. METHODS: Validated data from the Scottish National Health Service Medical Record Linkage Database were used to define a cohort of 12,584 patients undergoing open lower abdominal surgery in 1986. Readmissions for potential adhesion-related disease in the subsequent ten years were analyzed. The methodology was conservative in interpreting adhesion-related disease. RESULTS: In the study cohort 32.6 percent of patients were readmitted a mean of 2.2 times in the subsequent ten years for a potential adhesion-related problem. Although 25.4 percent of readmissions were in the first postoperative year, they continued steadily throughout the study period. After open lower abdominal surgery 7.3 percent (643) of readmissions (8,861) were directly related to adhesions. This varied according to operation site: colon (7.1 percent), rectum (8.8 percent), and small intestine (7.6 percent). The readmission rate was assessed to provide an indicator of relative risk of adhesion-related problems after initial surgery. The overall average rate of readmissions was 70.4 per 100 initial operations, with 5.1 directly related to adhesions. This rose to 116.4 and 116.5, respectively, after colonic or rectal surgery-with 8.2 and 10.3 directly related to adhesions. CONCLUSIONS: There is a high relative risk of adhesion-related problems after open lower abdominal surgery and a correspondingly high workload associated with these readmissions. This is influenced by the initial site of surgery, colon and rectum having both the greatest impact on workload and highest relative risk of directly adhesion-related problems. The study provides sound justification for improved adhesion prevention strategies.

Prevention of severe ovarian hyperstimulation syndrome in IVF with or without ICSI and embryo transfer: a modified 'coasting' strategy based on ultrasound for identification of high-risk patients.

Ovarian hyperstimulation syndrome (OHSS) can be a severe and potentially life-threatening complication of ovarian stimulation for IVF. Coasting or withholding gonadotrophin stimulation relies on frequent estimation of serum oestradiol to identify patients at risk. A modified coasting protocol was developed in which identification of patients at risk of severe OHSS was based on ultrasound monitoring. Serum oestradiol concentrations were measured only in patients with >20 follicles on ultrasound (high risk). If serum oestradiol concentrations were <3000 pmol/l, the gonadotrophin dose was maintained; if concentrations were >/=3000 pmol/l but <13200 pmol/l and >/=25% of the follicles had a diameter of >/=13 mm, the gonadotrophin dose was halved; and if serum oestradiol concentrations were >/=13 200 pmol/l and >/=25% of the follicles had a diameter of >/=15 mm, patients were coasted. In the latter group, human chorionic gonadotrophin (HCG) 10000 IU was administered when at least three follicles had a diameter of >/=18 mm and serum oestradiol concentrations were <10000 pmol/l. Over a 10 month period, serum oestradiol concentrations were measured in 123 out of 580 cycles (24%) and in 50 cycles, gonadotrophins were withheld. Overall, moderate OHSS occurred in three patients (0.7%) and severe OHSS in one patient (0.2%). The pregnancy rates in the cycles where the gonadotrophin dose was reduced or withheld were 39.6 and 40% per cycle respectively; corresponding implantation rates were 30.7 and 25.6%. It is concluded that the modified coasting strategy is associated with a low risk of moderate and severe OHSS to a minimum without compromising pregnancy rates. Identification of patients at risk by ultrasound reduces the number of serum oestradiol measurements and thus inconvenience to patients as well as costs and workload.

Does laparoscopic ovarian diathermy affect the outcome of IVF-embryo transfer in women with polycystic ovarian syndrome? A retrospective comparative study.

Controlled ovarian stimulation for IVF and embryo transfer and outcome parameters were compared retrospectively in 31 women with clomiphene-resistant polycystic ovarian syndrome (PCOS). Of these women, 15 had previously undergone laparoscopic ovarian diathermy before IVF (group A, total 22 cycles) and 16 had not had surgical treatment (group B, total 24 cycles). No statistically significant differences were observed in the number of oocytes retrieved, although the number of embryos available for transfer was significantly higher in group B (7.1 +/- 3.8 versus 4.6 +/- 2.7, P < 0.01). The clinical pregnancy rate per embryo transfer appeared to be higher in group B (63.2 versus 41.2%), as did the miscarriage rate (66.7 versus 28.6%), giving an apparent improved ongoing pregnancy rate per embryo transfer in group A (29.4 versus 10.5%), but this was not statistically significantly different. The incidence of severe ovarian hyperstimulation syndrome (OHSS) was apparently higher in group B (4.2 versus 0%), but this difference was not statistically significant. No cases of severe OHSS were seen in group A. Ovarian diathermy does not appear to have a deleterious effect on controlled ovarian stimulation, and the outcome of IVF-embryo transfer may be beneficial in decreasing the risk of severe OHSS and improving the ongoing clinical pregnancy rate.

The impact of adhesions on hospital readmissions over ten years after 8849 open gynaecological operations: an assessment from the Surgical and Clinical Adhesions Research Study.

OBJECTIVE: To investigate the epidemiology of, and the clinical burden related to, adhesions following gynaecological surgery. POPULATION: The Scottish National Health Service Medical Record Linkage Database was used to define a cohort of 8849 women undergoing open gynaecological surgery in 1986. METHODS: All readmissions for potential adhesion related disease in the subsequent 10 years were reviewed. MAIN OUTCOME MEASURES: Readmissions and the degree of adhesion involvement gave an indication of clinical burden and workload. The rate of readmission following the initial surgery determined the relative risk of disease related to adhesions. RESULTS: Two hundred and forty-five (4.5%) of 5433 readmissions following open gynaecological surgery were directly related to adhesions. 34.5% of patients were readmitted, on average 1.9 times, for a problem potentially related to adhesions or for further intra-abdominal surgery that could be complicated by adhesions. Readmissions related to adhesions continued throughout the 10 year period of the study. The overall rate of readmission was 64.0/100 initial operations. For readmissions directly related to adhesions, the rate was 2.9/100 initial operations. Operations on the ovary had the highest rate directly related to adhesions (7.5/100 initial operations), with an overall rate of readmission of 106.4/100 initial operations. CONCLUSIONS: Despite the conservative approach taken in this study, the clinical burden, workload and relative risk of readmissions related to adhesions following open gynaecological surgery was considerable. Post-operative adhesions have important consequences for patients, surgeons and the healthcare system. These results emphasise the need for more effective strategies to prevent adhesions.

Does pretreatment with progestogen or oral contraceptive pills in low responders followed by the GnRHa flare protocol improve the outcome of IVF-ET?

PURPOSE: Women undergoing in vitro fertilization with low ovarian reserve and poor response to controlled ovarian hyperstimulation (COH) present a management dilemma. In a retrospective observational study, we compared the pretreatment use of the gestogen medroxyprogesterone acetate (10 mg twice daily from day 15 of the cycle for a minimum of 2 weeks) with an oral contraceptive pill (one tablet daily from day 4 of the cycle for a minimum of 3 weeks). METHODS: The criteria for inclusion in the study included one or more of the following: abandoned cycles due to poor response, fewer than four oocytes retrieved following a standard COH protocol, age > 39 years, and elevated basal serum follicle-stimulating hormone (FSH). Thirty-eight women received pretreatment with gestogen, and a similar number of women received pretreatment with the pill. The flare protocol was used in all treatment cycles combined with an individualized dose of human menopausal gonadotropin (hMG) (4-8 ampoules/day of 75 units FSH/ampoule) depending on previous response, age, and early follicular serum FSH level. Both groups were similar in mean age, duration of infertility, early follicular FSH levels, and the distribution of various aetiologies. RESULTS: Twenty-nine cycles were abandoned before oocyte retrieval, 15 (39.5%) in the pill group and 14 (36.8%) in the gestogen group, because of an inadequate ovarian response. The mean (+/- SD) number of ampoules (75 IU FSH/ampoule) of hMG used per cycle was similar in the pill and gestogen groups (59.7 +/- 19.3 vs. 70.2 +/- 29.4, respectively). There also was no difference seen in the numbers of oocytes retrieved (4.4 +/- 2.3 vs. 4.2 +/- 2.5), total number of embryos (2.5 +/- 2.4 vs. 2.2 +/- 1.1), or the number of embryos transferred (1.8 +/- 1.2 vs. 2.1 +/- 1.0) in the pill and gestogen groups, respectively. One pregnancy in each group resulted following embryo transfer in 22 women in the pill group and in 24 women in the gestogen group. CONCLUSIONS: We conclude that pre-IVF treatment with oral contraceptive pill or gestogen combined with the flare protocol in women at high risk of or with a history of poor ovarian response, as defined in this study, did not appear to result in an improvement in outcome of IVF-embryo transfer.

New directions in the prevention of adhesion in laparoscopic surgery.

The aim of this review is to appraise critically the literature over the past year with respect to new developments in adhesion prevention strategies. The majority of the work continues to be focused on animal models, and interest continues into the usage of heterologous barriers, which are increasingly derived from or related to hyaluronic acid. The recent trend has been to develop barriers that are not only effective but also technically easy to use for the laparoscopic surgeon--hence the development of barrier gels. It is only through the development of these user-friendly barriers that many laparoscopic surgeons will be willing to incorporate these important preventative measures into their busy daily practice. Routine usage of adhesion prevention measures will ultimately reduce patient morbidity and mortality and relieve the burden on health service provision.

Adhesion-related hospital readmissions after abdominal and pelvic surgery: a retrospective cohort study.

BACKGROUND: Adhesions after abdominal and pelvic surgery are important complications, although their basic epidemiology is unclear. We investigated the frequency of such complications in the general population to provide a basis for the targeting and assessment of new adhesion-prevention measures. METHODS: We used validated data from the Scottish National Health Service medical record linkage database to identify patients undergoing open abdominal or pelvic surgery in 1986, who had no record of such surgery in the preceding 5 years. Patients were followed up for 10 years and subsequent readmissions were reviewed and outcomes classified by the degree of adhesion. We also assessed the rate of adhesion-related admissions in 1994 for the population of 5 million people. FINDINGS: 1209 (5.7%) of all readmissions (21,347) were classified as being directly related to adhesions, with 1169 (3.8%) managed operatively. Overall, 34.6% of the 29,790 patients who underwent open abdominal or pelvic surgery in 1986 were readmitted a mean of 2.1 times over 10 years for a disorder directly or possibly related to adhesions, or for abdominal or pelvic surgery that could be potentially complicated by adhesions. 22.1% of all outcome readmissions occurred in the first year after initial surgery, but readmissions continued steadily throughout the 10-year period. In 1994, 4199 admissions were directly related to adhesions. INTERPRETATION: Postoperative adhesions have important consequences to patients, surgeons, and the health system. Surgical procedures with a high risk of adhesion-related complications need to be identified and adhesion prevention carefully assessed.

Routine use of saline hysterosonography in 500 consecutive, unselected, infertile women.

Saline hysterosonography was attempted as a routine, first-line screening test of uterine structure in 500 consecutive, unselected, infertile women. The procedure was completed in 96.8% (484/500) women and the observations were interpretable in 483 of these women. Intrauterine pathology was suspected in 67/499 (13.4%) women on plain ultrasound scan and 58/484 (12%) women with saline hysterosonography. Ultrasound alone had a superior specificity (96.3%) to sensitivity (81.8%) and better negative (97.6%) than positive (73.8%) predictive value for the detection of any intrauterine abnormality, using saline hysterosonography as the reference procedure. Suspected pathology at saline hysterosonography led to hysteroscopy in 20 women, after a median of 5.7 months (range, 1-14). The overall concordance rate between the two procedures was 65% with lesions suspicious of intrauterine polyps not present at subsequent hysteroscopy on six occasions. Criteria were established to help identify women with potentially self-limiting lesions, in whom a re-scan should be considered before resorting to hysteroscopy. The procedure was well tolerated with no significant complications. Saline hysterosonography appeared to be an acceptable first-line screening procedure for uterine structure which enhanced the predictive power of ultrasound alone for uterine anomalies and provided additional information which was potentially of value when planning operative hysteroscopy.

Effect of smoking on ovarian reserve and ovarian stimulation in in-vitro fertilization and embryo transfer.

The effect of cigarette smoking on ovarian reserve as measured by basal serum follicle stimulating hormone (FSH) concentrations, and by the response to a standard ovarian stimulation protocol, was examined retrospectively in 173 consecutive women (108 non-smokers and 65 smokers) undergoing in-vitro fertilization (IVF) and embryo transfer treatment. Women who smoked had a higher mean basal serum FSH concentration (P < or = 0.0001), in particular younger (<36 years) women, and required a statistically significantly higher mean dosage of gonadotrophins for ovarian stimulation than the non-smokers (48.1 +/- 15.6 versus 38.9 +/- 13.6 ampoules, 75 IU/ampoule; P < 0.0001). A lower mean number of oocytes was obtained in smokers than non-smokers (6.2 +/- 3.4 versus 11.1 +/- 6.3, oocytes P < or = 0.0001) and the rate of abandoned cycles (18.5 versus 8.5%) and total fertilization failure (18.5 versus 8.5%) was higher. The clinical pregnancy rate per cycle in smokers was 16.9% versus 21.3% in non-smokers but this was not statistically significant. In conclusion, cigarette smoking in women appears to significantly reduce their ovarian reserve and lead to poor response to ovarian stimulation at an earlier age.

Evaluation of the performance of hysterosalpingo contrast sonography in 500 consecutive, unselected, infertile women.

The performance of hysterosalpingo contrast sonography (Hy Co Sy) as a first-line, outpatient investigation of tubal patency was examined in 500 consecutive, infertile women, at one centre. Hy Co Sy was completed in 463 (92.6%) cases, using a galactose microbubble contrast agent (Echovist-200) and transvaginal sonography. Initial plain scanning identified adnexal pathology in 198 women (39.6%). Examination with Echovist was attempted for 905 tubes and only 67 (7.4%) were not assessable; after the first 100 women this decreased to 35 tubes (4.8%). A sonographic appearance compatible with blocked tubes was found on 118 (14.1%) occasions but it was also possible to identify variations in the appearance/filling/spilling patterns of individual tubes which increased the number assessed as abnormal to 193 (23.0%). Comparison with laparoscopy and dye chromopertubation findings from the past three years was possible for 185 (37%) women, representing 282 tubes, which gave Hy Co Sy an overall concordance rate of 85.8%, sensitivity of 90.4%, specificity of 70.3%, positive predictive value of 91.2% and negative predictive value of 68.2%. Some 51.0% of women described only mild discomfort and there were no significant postprocedure complications. Hy Co Sy appears to be an acceptable first-line screen and may select out women in whom more invasive investigations are likely to reveal pathology.

Attitudes towards routine human immunodeficiency virus (HIV) screening and fertility treatment in HIV positive patients--a UK survey.

Of 70 fertility units licensed by the Human Fertilisation and Embryology Authority in the UK, 58 responded to a questionnaire regarding attitudes towards human immunodeficiency virus (HIV) screening and fertility treatment in HIV positive patients in November 1995. Of these 58 centres, 23 only performed routine screening for HIV for both partners, 24 for hepatitis B and eight for hepatitis C. In the event of a positive result in the male, fertility treatment would be offered in the form of donor insemination (n = 21), intrauterine insemination (IUI) after sperm washing (n = 21), and in-vitro fertilization (IVF) (n = 1). If the woman was HIV positive, two centres would offer IUI and three centres IVF. Nine centres had already provided treatment for couples in whom the male partner was HIV positive and two centres to HIV positive women.

Concentrations of placental protein 14 in uterine flushings from infertile women: validation of the collection technique and method of expression of results.

Concentrations of various proteins in uterine flushings have been described as a direct method for assessment of the secretory activity of the endometrium. We investigated levels of the endometrial protein known as placental protein 14 (PP14) in flushings obtained from 271 infertile women. Under transvaginal ultrasonographic control, 2 ml of 0.154 M sodium chloride solution were injected into the uterine cavity and re-aspirated, five times. In contrast to previous studies the recovered volume of each flushing was not consistent (range: 0.05-2.1 ml); the volume varied significantly between serial samples obtained from an individual (P = 0.02, one-way ANOVA), different cycle days (P < 0.0001, one-way ANOVA) and women with bilaterally blocked versus patent Fallopian tubes (P < 0.05, Student's t-test). Concentrations of PP14 showed a better correlation with protein content (r = 0.506, P < 0.0001) than with the recovered volume (r = 0.087, P = 0.095). We therefore corrected PP14 concentrations for total protein content as an indicator of the efficiency of the flushing process. Corrected PP14 concentrations varied significantly relative to time since the onset of menstruation (P = 0.001, Kruskal Wallis ANOVA) with higher levels on days 1-8, as previously observed in plasma samples. No significant difference in PP14 levels was found with different causes of infertility. This study shows that uterine flushing is not a consistent process in women with differing physical characteristics and at varying times throughout the menstrual cycle.