A double-blind randomised study comparing danazol and medroxyprogesterone acetate in the management of menorrhagia.

A randomised study was undertaken comparing danazol 200 mg daily and medroxyprogesterone acetate 10 mg daily from days 16 to 25 in the management of menorrhagia. Twenty-three women were recruited to the study over a 12-month period. Eighteen subjects were suitable for analysis. Three months' therapy was given and patients were observed for a 3-month period following discontinuation of therapy. Menstrual blood loss was estimated during initial patient assessment and then during each of the 6 months of the study. In the danazol group mean blood loss at all treatment phase months was significantly decreased from baseline. In contrast, blood loss was not reduced significantly in any study month when compared with baseline in the medroxyprogesterone acetate group. During the post-treatment phase the mean blood loss in the danazol group increased to above normal levels but remained significantly lower than baseline, and there was a significant reduction in menstrual blood loss in the medroxyprogesterone acetate group.

Impact of the learning curve on term delivery rates following laparoscopic salpingostomy for infertility associated with distal tubal occlusive disease.

The objective of this study was to determine the impact of the learning curve of one surgeon on the term delivery rate following laparoscopic salpingostomy for tubal infertility. This was a retrospective audit of ongoing clinical practice, undertaken in two tertiary level infertility programmes. Subjects in this study were women undergoing surgery for total occlusion of the distal Fallopian tube. The main outcome measure was cumulative term delivery rates. On stepwise life-table analysis the length of infertility, primary and secondary infertility, tubal diameter and whether surgery was performed in the first or second half of the series were significantly associated with outcome. These data suggest that there is a learning curve in obtaining skills to perform laparoscopic salpingostomy, that patient selection may improve with experience, and that selection criteria should be emphasized during didactic teaching and the preceptorship process.

The production of leukaemia inhibitory factor by human endometrium: presence in uterine flushings and production by cells in culture.

The concentration of leukaemia inhibitory factor (LIF) was measured in uterine flushings obtained from normal fertile women, from women with unexplained infertility and from women who suffered recurrent miscarriage. In normal fertile women, LIF was not detected in flushings obtained on days luteinizing hormone (LH)+0 to LH+6 of the cycle, but concentrations gradually increased from day LH+7 to a maximum at day LH+12. The amount of LIF in flushings obtained from women with unexplained infertility was significantly lower than in those from normal fertile women on day LH+10 (P < 0.05). The production of LIF by cultured human epithelial and stromal cells was also investigated. LIF was not detectable in the supernatants of cultured stromal cells. Basal LIF production by epithelial cells varied according to the stage in the cycle at which the biopsy was taken. Significantly more LIF was produced by epithelial cells from late proliferative and early secretory endometrium compared with amounts produced by cells from early proliferative (P < 0.001) and late secretory (P < 0.01) endometrium. High doses of progesterone and oestradiol caused a small decrease in epithelial cell LIF production: the combined effect of progesterone and oestradiol (P < 0.01) was greater than the effect of either steroid alone (P < 0.05). The results show, for the first time, the capability of human endometrium to produce LIF in vivo. The fact that maximum LIF concentrations are present at implantation and that decreased concentrations occur in women with unexplained infertility suggest the importance of this cytokine in embryo implantation.

Outcome study using an administrative database: terminal salpingostomy, physician case load and live birth rates.

Information on the outcome following salpingostomy performed for infertility in everyday practice is needed to counsel patients, determine the best approach to this condition and clarify whether the outcome is superior when surgery is performed by a physician who maintains a high volume of ongoing experience. A total of 547 consecutive subjects were identified over a 5 year period using the Alberta Health Care Claims Database. Their claims history was analysed over a follow-up of 2-7 years, to identify pregnancy-related events, loss to follow-up and events which would result in sterility. Pregnancies were cross-checked with the only in-vitro fertilization programme serving the region. The overall cumulative live birth and tubal pregnancy rates were 11.7 and 7.2% respectively. Live birth rates were significantly higher when practitioners had performed >10 procedures within the study period. Live birth rates would appear to be substantially lower in everyday practice than following surgery performed by acknowledged experts. A high volume of ongoing experience appears to be associated with superior live birth rates. It is unclear whether this association relates to case selection, surgical expertise or both variables.

Falloposcopic cannulation, oviductal appearances and prediction of treatment independent intrauterine pregnancy.

The purpose of this study was to determine whether there is an association between the appearance of the oviductal lumen during falloposcopic examination, and the occurrence of intrauterine pregnancy or ectopic pregnancy independent of treatment. Sixty-two consecutive women were recruited who were examined falloposcopically in-office, and who did not require subsequent surgical intervention to restore tubal patency. There was a heterogeneous group of presentations including unilateral and bilateral proximal tubal occlusion, unexplained infertility and the presence of minor laparoscopic abnormalities which might suggest the possibility of occult endotubal pathology. A stepwise Cox's model of life table analysis selected the number of falloposcopically normal and patent Fallopian tubes as the only variable significantly associated with intrauterine pregnancy, when all clinical, demographic and investigative data were analysed. The presence of minor distal intra-tubal adhesions was selected on stepwise analysis as the only variable significantly associated with the occurrence of ectopic pregnancy. A number of falloposcopic abnormalities were significantly associated with outcome in the clinical sub-group who presented with bilateral proximal tubal occlusion. These data suggest that falloposcopy is a valuable clinical tool which provides useful prognostic data for the prediction of intrauterine pregnancy or ectopic pregnancy.

Human embryo implantation following in-vitro fertilization: is there a seasonal variation?

The purpose of this study was to determine whether there is a seasonal variation in implantation and pregnancy rates following natural cycle replacement of cryopreserved embryos. A total of 321 consecutive cycles were analysed. There were 59 pregnancies (18.4%) and 48 live births or ongoing pregnancies (15.0%). Indicator variables for each month and variables representing temporal cycles of 12, 6, 4, 3 and 2 months were related to outcome. In addition, an analysis of periodicity was performed. No temporal, clinical or demographic variable was significantly related to pregnancy. This study indicated that there was no clear seasonal variation in the pregnancy rate following natural cycle replacement. However, the power of this study was low, and it was estimated that 963 subjects would be required to detect a 10% seasonal difference in pregnancy rates.

Outcome of thaw embryo transfer after cryopreservation of all embryos in patients at risk of ovarian hyperstimulation syndrome.

OBJECTIVE: To determine the incidence of ovarian hyperstimulation syndrome (OHSS) and subsequent pregnancy rates (PRs) if ET is delayed in patients at risk of OHSS by allocating all embryos to cryopreservation. DESIGN: Retrospective analysis of clinical and laboratory data from 724 consecutive stimulated cycles of IVF. SETTING: University hospital-based IVF program. PATIENTS: Consecutive patients undergoing IVF between September 1989 and December 1992. MAIN OUTCOME MEASURES: Fertilization rates, cryosurvival rates, subsequent PRs, and the occurrence of severe OHSS. RESULTS: Ten of the 564 patients (1.8%) who had ET in the stimulation cycle developed severe OHSS. Sixty-nine patients had all embryos frozen because of the risk of OHSS, of which one (1.4%) developed severe OHSS. The subsequent PR after thaw transfer was 25.2% per transfer, with a cumulative PR per patient after additional thaw transfers of 40.6%. CONCLUSIONS: Cryopreservation of all embryos and delayed ET in patients at risk of OHSS results in a low incidence of severe OHSS. Oocyte quality, fertilization rates, and cryosurvival of frozen embryos are equal to those for patients who have a normal stimulation profile. Subsequent thaw embryo replacements result in a satisfactory PR.

Cervical pregnancy following in vitro fertilization: evacuation after uterine artery embolization with subsequent successful intrauterine pregnancy.

A case is described in which a cervical pregnancy followed in vitro fertilization. Treatment was delayed at the request of the patient until the second trimester, and was successfully managed by preoperative bilateral angiographic uterine artery occlusion, surgical evacuation, and postoperative balloon tamponade. Subsequent embryo transfer of previously cryopreserved embryos resulted in a normal intrauterine pregnancy and delivery without complications. This case highlights the need for awareness of cervical pregnancy following in vitro fertilization and the success of management which preserves fertility.

Comparison of ampullary assessment by falloposcopy and salpingoscopy.

The purpose of this study was to compare and contrast falloposcopic and salpingoscopic ampullary assessments in a series of 20 women undergoing tubal microsurgery for distal tubal or peritubal disease. Four women had an extrinsic cause for their peritubal adhesions, and would have been expected to exhibit a normal oviductal canal. All of the falloposcopic examinations were performed as an outpatient procedure. Salpingoscopic examinations were undertaken at the time of microsurgery. The endoscopic examinations were undertaken by two clinicians, who were blinded to each other's assessments and to the indication for surgery. Of the 31 Fallopian tubes which were examined, 24 were found to be abnormal by salpingoscopy and 23 were found to be abnormal by falloposcopy. Total score and scores for epithelial appearance, vascularity, intraluminal adhesions and dilatation were found to be significantly associated. Furthermore, falloposcopy predicted salpingoscopic status correctly in 84% of cases. These data suggest that falloposcopy is a useful method of assessing ampullary condition.

Failed reversal of sterilization: transcervical transostial recannulation of occluded fallopian tube.

A patient with bilateral occlusion at the site of tubal reanastomosis demonstrated the potential benefits and hazards of attempted transcervical transostial tubal cannulation to restore patency. On one side tubal patency was restored, whereas on the other a false passage was created distal to the reanastomosis.

PIP: This article reports on a case in which a 44-year-old woman had requested correction of possibly blocked fallopian tubes. The woman had previously had two normal vaginal deliveries and had subsequently undergone a Pomeroy tubal ligation following the birth of her second child. Nine years later she underwent a tubal reattachment procedure in an effort to reverse the sterilization. Bilateral tubal patency was demonstrated 2 months post-surgery, and 8 months later she conceived. This pregnancy, however, ended in a spontaneous abortion that required curettage. She could not conceive from that time to the time of her visit to the physician. Subsequent investigation revealed normal progesterone levels, semen analysis, and fallopian tubes. No pelvic adhesions or endometriosis were found. At that time, the patient requested tubal cannulation. She was counseled on the possible complications of pregnancy and on the tubal cannulation procedure. The procedure was performed using falloposcopy to visually confirm cannulation. Falloposcopy was performed with a linear eversion catheter. Concomitant laparoscopy was also used to visually confirm cannulation. After falloposcopy, perhydrotubation was performed; tubal patency was confirmed on the right side but not on the left. Creation of a false passage on the left side was successful. This case shows the potential merits and hazards of tubal patency restoration by transcervical transostial cannulation of an occluded oviduct following a reversal of sterilization.

Factors predicting outcome in 215 consecutive thawed embryo replacements.

This retrospective study was undertaken to determine which factors were associated with outcome in thawed embryo replacement cycles. The number of embryos replaced and the response to exogenous ovarian stimulation in the original IVF cycle were significantly associated with the conception rate.

Falloposcopic comparison of unilateral and bilateral proximal tubal occlusive disease.

The purpose of this study was to compare the appearance of the entire length of the oviductal canal in women with unilateral versus bilateral proximal tubal occlusion. Eleven women had apparent unilateral disease and 18 had apparent bilateral occlusion. Proximal occlusion was confirmed both by hysterosalpingography and laparoscopy. Falloposcopic examination was performed by retrograde visualization using the linear eversion catheter, in office. Bilateral apparent proximal occlusion was found to have a significantly higher incidence of actual proximal occlusion and distal intralumenal abnormalities. However, five proximal segments and six distal segments were found to be abnormal where the pre-examination diagnosis was unilateral occlusion. Furthermore, the contralateral oviductal canal was found to be abnormal in four women with apparent unilateral disease, indicating that apparent unilateral proximal tubal occlusion is associated with actual pathology. These data demonstrate the value of intralumenal assessment of apparent proximal occlusion.

Office falloposcopic assessment in proximal tubal occlusive disease.

Intraluminal images were reliably obtained by office falloposcopy in the presence of proximal tubal occlusion. Although there were associations between data obtained at laparoscopy and intralumenal appearances, these relations were not uniform, indicating that there may be a role for falloposcopic assessment in planning the management of proximal tubal occlusion. A prospective study is advocated to assess the linear eversion catheter as a therapy for proximal tubal occlusion.

Prognostic value of two putative sperm function tests: hypo-osmotic swelling and bovine sperm mucus penetration test (Penetrak).

The clinical value of two inexpensive and easy to perform sperm function tests (hypo-osmotic swelling and bovine sperm mucus penetration tests) were examined in a prospective study of in-vivo conception rates in 325 couples. Both tests were of no significant value alone or in combination with traditional semen characteristics in predicting pregnancy outcome. The two most predictive factors of conception were the length of infertility and percentage of progressively motile spermatozoa. Our data support the further investigation of sperm function using more sophisticated quantitative tests, specifically the examination of sperm motility.

Outpatient falloposcopy: intra-luminal imaging of the fallopian tube by trans-uterine fibre-optic endoscopy as an outpatient procedure.

OBJECTIVE: To develop trans-uterine falloposcopy using the linear eversion technique in outpatients. DESIGN: A prospective, descriptive study of the introduction and application of this new technique. SETTING: A tertiary referral University Research Clinic independent of operating theatres and inpatient admission. SUBJECTS: Twenty-one infertile women with previous evidence of fallopian tube disease. MAIN OUTCOME MEASURES: Rate of successful tubal cannulation and procedure completion, tubal section visualized, condition of the tubal epithelium, subsequent treatment plan. RESULTS: A bilateral examination was attempted in 19/21 patients and completed in 18. Two early falloposcopies with inadequate analgesia were aborted due to pain after only one tube had been examined without an attempt to identify or cannulate the contralateral tubal ostium. In one patient, neither ostium was identified or cannulated. After ostial localization, 37/37 tubes were cannulated. If the ostium was not localized but 'blind' cannulation attempted, 1/3 were cannulated successfully. Epithelium characteristic of the ampulla was seen in 31/38 (82%) tubes, and of the proximal tube only in 3/38 (8%). Successful bilateral assessment noted complete bilateral proximal obstruction in 2/18 patients, non-obstructive bilateral endotubal damage in 7/18, unilateral damage in 3/18 and bilateral healthy tubes in 6/18. Unilateral examination in two patients found minimal evidence of damage in one and severe intra-tubal adhesions in the other. After falloposcopy, 11/21 patients elected for IVF, 9/21 tubal surgery and 1/21 for IVF whilst awaiting surgery. CONCLUSION: Falloposcopy is a technique which can be performed in an outpatient clinic. It is well tolerated, and high rates of luminal cannulation and visualization are possible. Atraumatic access to the tube and visualization of its lumen offer exciting opportunities for diagnosis and treatment of tubal conditions.

The poor prognostic value of low to moderate levels of sperm surface-bound antibodies.

The clinical significance of antisperm antibodies for fertility remains controversial. In this study, we determined whether the presence, isotype, region and/or amount of sperm-bound antibody was of any predictive value for future fertility in 534 men using Cox's proportional hazards model. Significant correlations between the presence of antibodies and semen parameters were recorded, such as sperm mucus penetration and sperm motility. However, low (less than 10%) negative binding and moderate (less than 50%) binding had no significant effect on the probability of conception or the time to conception. This study confirms in-vitro data suggesting that sperm function is not impaired unless the degree of antibody binding to spermatozoa is very high.

Male alcohol consumption and fecundity in couples attending an infertility clinic.

The relationship between male alcohol intake and fertility was studied for 258 couples attending an infertility clinic. 21% consumed less than 1 unit per week on average, 10% consumed between 1 and 5 units per week, 23% consumed between 6 and 10 units per week, 27% consumed 11 to 20 units per week and 19% consumed more than 20 units per week. There was no significant association between alcohol consumption and any semen parameter. 110 men had a female partner who was apparently normal. There was no significant difference in the alcohol intake between the 'normal' and 'abnormal' female groups. Couples were followed-up for up to 32 months. Sixteen women had a treatment independent conception within the 'normal' female group. There was no significant association between the amount of alcohol consumed per week and the fertility outcome.

Male cigarette smoking and fecundity in couples attending an infertility clinic.

The relationship between male cigarette smoking and fertility was studied for 330 couples attending an infertility clinic. 59% did not smoke, 10% smoked between 1 and 5 per day, 8% smoked between 6 and 10 per day, 16% smoked 11-20 per day and 7% smoked more than 20 per day. There was no significant association between smoking and any semen parameter. 138 men had a female partner who was apparently normal. There was no significant difference in smoking habits between the 'normal' and 'abnormal' female groups. Couples were followed-up for up to 32 months. Nineteen women had a treatment independent conception within the 'normal' female group. There was no significant association between the number of cigarettes smoked and the fertility outcome.

The importance of employing stringent methods to recruit fertile male controls.

Two methods of recruiting fertile male controls were evaluated and compared. The first group was recruited from the partners of women attending an antenatal clinic without obtaining details of their reproductive history. The second group was recruited after obtaining a detailed reproductive history from the couple and employing stringent entry criteria. Entry criteria for the second group included a length of exposure to the risk of pregnancy of not more than 12 months and no previous episode of involuntary infertility for either partner. There were significant differences between the distributions of semen parameters obtained from the two groups, indicating that the selection criteria for "fertile" men significantly influence results obtained and therefore that it is important to employ stringent criteria for the recruitment of fertile male controls. The group which was recruited by stringent criteria (mean length of exposure to the risk of pregnancy of 3 months) was characterised by a significantly higher median concentration of spermatozoa which exhibited slow linear or nonlinear motility. This confirms the findings of a previous study which suggested that slow linear or nonlinear motility are superior forms of spermatozoal motion.

The placebo response of subfertile couples to attending a tertiary referral centre.

The objective of this study was to determine whether there was a placebo response to clinic attendance in couples with prolonged (greater than 4 years) subfertility. From 4 to 18 years of subfertility we observed a treatment independent cumulative conception rate of 22%, which was independent of the length of subfertility. Twenty-seven women conceived after 1 to 4 years' subfertility, and 30 conceived after greater than 4 years' subfertility. The fecundity of the latter group was significantly greater than that of women with 1 to 4 years' subfertility, being similar to "normal" subjects who had stopped contraception. This study demonstrates that a subgroup of apparently normal women with greater than 4 years' subfertility responded positively to clinic attendance independent of any investigation(s) or therapy.