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Previous work has suggested an association between male subfertility and a female-biased offspring sex ratio. This study of the reproduction of men who had a semen analysis at the Sperm Analysis Laboratory in Copenhagen in the period 1963-1993 showed that the subfertile men had an offspring sex ratio as expected (51.0% boys versus 51.3%, P: = 0.56), and within the cohort, the offspring sex ratio had no material association with particular semen characteristics. Our results thus suggest that no important association exists between general male subfertility and a female-biased offspring sex ratio.

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OBJECTIVE: To explore the associations between semen characteristics and subsequent risk of testicular cancer. DESIGN: Cohort study. PARTICIPANTS: 32 442 men who had a semen analysis done at the Sperm Analysis Laboratory in Copenhagen during 1963-95. MAIN OUTCOME MEASURE: Standardised incidence ratios of testicular cancer compared with total population of Danish men. RESULTS: Men in couples with fertility problems were more likely to develop testicular cancer than other men (89 cases, standardised incidence ratio 1.6; 95% confidence interval 1.3 to 1.9). The risk was relatively constant with increasing time between semen analysis and cancer diagnosis. Analysis according to specific semen characteristics showed that low semen concentration (standardised incidence ratio 2.3), poor motility of the spermatozoa (2.5), and high proportion of morphologically abnormal spermatozoa (3.0) were all associated with an increased risk of testicular cancer. The only other cancer group that showed increased incidence was "peritoneum and other digestive organs" (six cases; 3.7, 1.3 to 8.0). Of these, two cases were probably and two cases were possibly extragonadal germ cell tumours. CONCLUSIONS: The results point towards the existence of common aetiological factors for low semen quality and testicular cancer. Low semen quality may also be associated with increased incidence of extragonadal germ cell tumours.

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Analysis of associations between testicular cancer, subfertility and offspring sex ratio (proportion of males born among newborns) was performed on 3530 Danish men, born 1945-1980, who developed testicular cancer in the period 1960-1993. As the basis of comparison we used the total population of Danish men born in the period 1945-1980 (n = 1 488 957) and their biological children (n = 1 250 989). Men who developed testicular cancer had, prior to the cancer diagnosis, a reduced fertility (standardized fertility rate ratio: 0.93, 95% confidence interval: 0.89-0.97) and a significantly lower proportion of boys (48.9%, P: = 0.02) compared with the general population (51.3%). The reduction in fertility was more pronounced in men with non-seminoma but the reduction in offspring sex ratio was independent of histological type. This confirms earlier results from less conclusive studies and indicates that testicular cancer, male subfertility and a female-biased sex ratio among new-born infants are characteristics of male reproduction that are linked by biological mechanisms.

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In an attempt to create uniform nationwide guidelines for the management of all stages of endometrial carcinoma, and to limit the use of adjuvant radiation therapy in stage I disease to high-risk patients only, a protocol was developed by the Danish Endometrial Cancer group (DEMCA). From September 1986 through August 1988, 1214 women in Denmark with newly diagnosed carcinoma of the endometrium have been treated according to this protocol. This figure represents all endometrial carcinomas diagnosed in Denmark during this two-year period. The primary treatment was total abdominal hysterectomy and bilateral salpingo-oophorectomy, no preoperative radiation therapy was delivered. In 1039 cases no macroscopic residual tumour and/or microscopic tumor tissue in the resection margins was found following surgery. Based on surgery and histopathology, these patients were classified as: P-stage I low risk (n = 641), P-stage I high risk (n = 235), P-stage II (n = 105) and P-stage III, Group 1 (n = 58). No postoperative radiation therapy was given to P-I low risk cases. P-I high risk, P-II, and P-III (Group 1) cases received external radiation therapy. Recurrence rate at 68-92 months follow-up was 45/641 (7%) in P-I low risk, 36/235 (15%) in P-I high risk, 30/105 (29%) in P-II, and 27/58 (47%) in P-III (Group 1) cases. Fifteen of 17 vaginal recurrences in P-I low risk cases were salvaged (mean observation time 61 months). In this population-based investigation it has been shown that P-stage low-risk patients are adequately treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy, and that no pre- or postoperative radiation therapy is necessary.

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Eight ureter lesions of the ureter occurred among 100 consecutive patients undergoing radical hysterectomy for cancer of the uterine cervix. The management of this problem is discussed, and treatment guidelines for the most commonly seen lesions are proposed. It is concluded that a more liberal use of ureteric stents or catheters should be considered so as to reduce the number of ureteric lesions occurring in connection with radical hysterectomy. Urological assistance should be sought for urological lesions recognized during or after such operations.

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The menopause is defined as cessation of menstruation, ending the fertile period. The hormonal changes are a decrease in progesterone level, followed by a marked decrease in estrogen production. Symptoms associated with these hormonal changes may advocate for hormonal replacement therapy. This review is based on the English-language literature on the effect of estrogen therapy and estrogen plus progestin therapy on postmenopausal women. The advantages of hormone replacement therapy are regulation of dysfunctional uterine bleeding, relief of hot flushes, and prevention of atrophic changes in the urogenital tract. Women at risk of osteoporosis will benefit from hormone replacement therapy. The treatment should start as soon after menopause as possible and it is possible that it should be maintained for life. The treatment may be supplemented with extra calcium intake, vitamin D, and maybe calcitonin. Physical activity should be promoted, and cigarette smoking reduced if possible. Women at risk of cardiovascular disease will also benefit from hormone replacement therapy. There is overwhelming evidence that hormone therapy will protect against both coronary heart disease and stroke, and there is no increased risk of venous thrombosis or hypertension. A disadvantage of hormone replacement therapy is an increased risk of forming gall-bladder stones and undergoing cholecystectomy. Unopposed estrogen therapy gives a higher incidence of endometrial cancer in women with an intact uterus, but the contribution of progestins for about 10 days every month excludes this risk. Breast cancer in relation to estrogen-progestogen therapy has been given much concern, and the problem is still not fully solved. If there is a risk, it is small, and only after prolonged use of estrogen (15-20 years). The decision whether or not to use hormone replacement therapy should, of course, be taken by the individual woman in question, but her decision should be based on the available scientific information. It is the opinion of the authors that the advantages of hormone replacement therapy far exceed the disadvantages. We suggest that every woman showing any signs of hormone deprivation should be treated with hormone replacement therapy. This includes women with subjective or objective vaso-motor symptoms, genito-urinary symptoms, women at risk of osteoporosis (fast bone losers), and women at risk of cardiovascular diseases.

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To investigate, in a population of women suspected of an ovarian mass, whether pelvic ultrasound (US) and US combined with US-guided fine needle biopsy (FNB) increased the detection rate and whether tumor specific diagnoses could be obtained, a cohort of 307 patients suspected of an ovarian mass underwent US examination as part of routine gynecologic work-up. In cases of solid or solid/cystic lesions a US guided FNB for histology as well as cytology was proposed. All 35 primary ovarian cancers, 6 of 7 secondary ovarian cancers, and 3 of 4 non-ovarian cancers were demonstrated on US. Among 17 cases with normal palpation and an ovarian mass on US, operation disclosed 3 ovarian cancers. FNB identified 24 of 27 primary ovarian cancers and 7 of 7 cancers of extra-ovarian origin. The use of US, in this study, increased the detection of masses in the pelvis and FNB provided a reliable verification.

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Three hundred eighty-five women treated with conization due to repeated CIN I, CIN II or CIN III of the cervix uteri have been followed up for 5 years. All cones were classified according to diagnosis and status of the resection margins. A significantly greater recurrence rate of 16.2% was found in the group with neoplasia in the resection margins, in contrast to 3.9% in the group with normal resection margins. However, 83.8% (75.4-92.2%) of patients with neoplasia in the resection margins can be expected to be free of recurrence after a 5-year postoperative follow-up period. Whether the non-free resection margins were endocervical, ectocervical or both, did not influence the recurrence rate. While the prevalence of non-free resection margins increased significantly with increasing dysplasia, this could not be found with increasing age. The risk of recurrence could not be correlated with the grade of dysplasia. We conclude that neoplasia in the resection margins of the cone represents an increased risk of recurrence. Therefore, we changed the normal smear check-up with a cotton-swab to smear with cyto-brush, supplemented with colposcopy in the non-free resection margin group, but it remains to be proven that this procedure is safer.

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OBJECTIVE: To develop a fertility prognosis model for infertile couples. DESIGN: Prospective follow-up study. PARTICIPANTS: In the period November 30, 1977 to June 1, 1985, 321 consecutive couples were investigated for infertility at Hvidovre University Hospital. Investigation of the female included detection of ovarian, cervical, and anatomic disorders, whereas in the male semen analysis and sperm penetration test (P-test) were performed. Altogether, 108 couples (34%) conceived, whereas 213 (66%) were observed for an average of 2.3 years without having achieved pregnancy. MAIN OUTCOME MEASURE: The Cox regression model was used to predict the time required to conceive based on informations provided by fertility investigations. RESULTS: Three of 16 prognostic variables (the period of infertility, the female infertility factor, and the P-test) possess significant prognostic information. The period of infertility and the P-test are best scored as continuous variables, whereas the female infertility factor are best categorized in four classes, i.e., normal, ovulation or cervical disorder, anatomic disorder, or a combination of disorders. CONCLUSIONS: The three prognostic variables are combined to form a prognostic index that predicts the fecundability of the individual infertile couple.

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Ultrasound examination was performed on 307 patients admitted to Herlev Hospital, Copenhagen, for suspicion of a pelvic tumor. Of these, 194 were operated on, 38 (19.6%) having a malignant tumor and 156 with benign conditions. A solid tumor was suspected in 72 patients on whom intravenous pyelography, barium enema, cystoscopy and rectoscopy were performed, although 11 did not undergo an intravenous pyelography and 12 did not undergo a barium enema. Intravenous pyelography, barium enema, rectoscopy and cystoscopy very seldom gave unsuspected information and never changed the indications for operation. Ultrasound examination of the kidneys, urinary tract, bowel system, liver and retroperitoneum as a complementary investigation to the gynecologic examination of the pelvic tumor gave the same information as did the barium enema, intravenous pyelography, rectoscopy and cystoscopy. Therefore, we conclude that these investigations should be carried out only in patients with symptoms from the urinary tract or the bowel system. Instead, we suggest that ultrasound examination of a pelvic mass also include an examination of the kidneys, urinary tract, bowel system, liver and retroperitoneum.

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Three hundred and twenty-one consecutive couples were investigated for infertility at Hvidovre University Hospital in the period from November 1977 to June 1985. The male partners were evaluated in two ways: the classical semen analysis, and the ability of sperm to penetrate fresh hen egg white, the P-test. A Cox regression analysis was used to describe the relation between these variables and fecundability, i.e. the time required to conceive. Four of thirteen variables--the number of morphologically normal spermatozoa, the number of motile spermatozoa, the P-test, and the man's age--each have significant relation to the fecundability. However, when covariation is considered, only the P-test and the man's age possess significant prognostic information, whereas the variables of the classical semen analysis do not. This indicates that the P-test may replace the classical semen analysis when trying to predict individual pregnancy probabilities. Finally, the P-test and the man's age are combined to form a prognostic index which predicts the fecundability of the male partner in the individual infertile couple.

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Using the Cox proportional hazard regression model on one material (group I = 765, 1950 to 1951) we have identified four variables of semen analysis with significant prognostic information about fertility. The four variables were combined into a model for establishing the probability of the individual male to achieve pregnancy as a function of time. This model is tested first on another material (group II = 321, 1977 to 1985). A Goodness-of-fit test indicates excellent agreement between the expectations from the model and the observed number of pregnancies in group II. Second, the two groups are pooled (= 1,086). Then only three variables give significant prognostic information about the time until pregnancy: (1) the man's age at semen analysis (years); (2) the percentage of morphologically normal spermatozoa (ln %); and (3) the degree of motility (good/poor). These three important variables enter into a new and better prognostic model.

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A randomized, double-blind, crossover study was carried out to compare purified urinary follicle-stimulating hormone (FSH) and human menopausal gonadotropin (hMG) for ovarian stimulation in polycystic ovarian syndrome (PCOS). Twelve patients were stimulated with FSH and hMG in three alternate cycles. FSH, luteinizing hormone (LH), estradiol, dihydroepiandrosterone sulphate, free and total testosterone, delta 5-androstenedione, sex hormone binding globulin, and ovarian volume were monitored during the stimulation. There was no difference between the dose of FSH and hMG necessary to induce preovulatory follicles in the individual patients. The mean increase of ovarian volume during stimulation with FSH and hMG was 120% and 129% respectively (no significant difference). Two patients became pregnant in the first cycle. Two other patients had delayed bleeding and positive serum-human chorionic gonadotropin. No significant difference was found in the endocrine changes during the two different stimulation methods. The LH/FSH ratio was normalized after a few days of treatment regardless of the type of stimulation. The size of the material does not permit a comparison of the efficacy of the two treatment schedules. Our clinical and ultrasonic observations do not support the theory that treatment of infertility in PCOS with FSH is more safe than with hMG.

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The benefit of routine hysterosalpingography (HSG) and pre- and postoperative laparoscopy in diagnosing and treating anatomical infertility was investigated in 115 women. The findings at HSG and laparoscopy were compared with the diagnoses obtained by laparotomy. Laparoscopy was significantly better than HSG in detecting adhesions. Both procedures were of equal value in assessing tubal pathology. Although HSG revealed additional findings in 5 per cent of cases, none of these needed operative correction. Postoperative laparoscopy, which was performed in 70 patients, did not affect the incidence of either intra- or extra-uterine pregnancy. It is concluded that all patients should be offered diagnostic laparoscopy. HSG and second-look laparoscopy should not be used routinely.

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The Cox proportional hazard regression model was employed on 765 infertile men whose semen had been analysed in 1950 and 1951 and who replied to a questionnaire 20 years later. Of nine clinical and laboratory variables evaluated, four possessed significant and independent prognostic information about the time required to conceive, when covariation between the variables was considered. They were: age of the man at semen analysis, percentage normal spermatozoa, percentage mobile spermatozoa, and the degree of motility. The four variables were combined to form a prognostic index, which permits prediction of individual pregnancy probability. The five variables which possessed no significant prognostic information were time from ejaculation to semen analysis, period of abstinence, existence of previous pregnancy, volume and sperm count. There was a satisfactory agreement between predicted and observed pregnancies in the present series. Thus, the index may prove clinically useful. However, its value must be established in other independent series.

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Regression toward the mean denotes circumstances, where extreme observations tend to normalize at repetition. The phenomenon is caused by random variation and may occur whenever mainly persons with extreme values are subject to repeated examinations. We furnish empirical evidence that the phenomenon may be quantitatively important in fertility research with regard to some, but probably not all indicators of semen quality.

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In a randomized study, 204 patients were allocated to either laser or cryo treatment for cervical intra-epithelial neoplasia (CIN). The patients were treated on an outpatient basis without anesthesia unless other conditions requiring anesthesia had to be dealt with at the same time. Both the laser and the cryo method were highly acceptable to the patients. Slightly more patients experienced moderate or severe pain during laser treatment, compared with cryo treatment (P = 0.05). Peroperative hemorrhage did not exceed 25 cc except for one laser-treated patient. Postoperative vaginal discharge was more often seen after cryo coagulation, the discharge being malodorous in 36% of cryo-treated patients and in 17% of laser-treated patients. Pelvic inflammatory disease was found in one patient in each treatment group. Postoperative spotting occurred more often in laser-treated patients (49%) than in cryo-treated patients (22%). At follow-up colposcopy 3 months after treatment, the squamocolumnar junction was fully visible significantly more often in laser-treated patients (P less than 0.001). The cure rates after one laser or cryo treatment were 90% and 91%, respectively. Subsequent to 19 initial treatment failures, 8 patients have at present been retreated with the same method as initially used, and all 8 are cured. The cure rates after one or two treatments are 96% in the laser group and 93% in the cryo group. The rates are preliminary, due to the short observation time. Publications will appear when all patients have been followed for 2 and 5 years.

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Three methods of episiotomy repair were randomly assigned after 900 consecutive deliveries. The three procedures were: (1) continuous No. 00-plain catgut in the vagina; No. 00-plain catgut interrupted stitches in the perineal muscles and fascia, and No. 00-nylon interrupted stitches in the skin. (2) The same technique as in (1), but with No. 0-polyglycolic acid (Dexon) in all layers. (3) The suture material as in (2), but used with a subcuticular technique. The women treated with method 3 reported statistically significant less pain and disabilities in the early puerperium. Three months after delivery 262 women (33%) still had perineal complaints which could be directly related to the episiotomy in 25% (8% of total number). The group treated with method 3 had the best long-term results and we conclude that the subcuticular technique using polyglycolic acid should be the method of choice.

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