Development of a core outcome set and outcome definitions for studies on uterus-sparing treatments of adenomyosis (COSAR): an international multistakeholder-modified Delphi consensus study.

STUDY QUESTION: What outcomes should be reported in all studies investigating uterus-sparing interventions for treating uterine adenomyosis? SUMMARY ANSWER: We identified 24 specific and 26 generic core outcomes in nine domains. WHAT IS KNOWN ALREADY: Research reporting adenomyosis treatment is not patient-centred and shows wide variation in outcome selection, definition, reporting and measurement of quality. STUDY DESIGN, SIZE, DURATION: An international consensus development process was performed between March and December 2021. Participants in round one were 150 healthcare professionals, 17 researchers and 334 individuals or partners with lived experience of adenomyosis from 48 high-, middle- and low-income countries. There were 291 participants in the second round. PARTICIPANTS/MATERIALS, SETTING, METHODS: Stakeholders included active researchers in the field, healthcare professionals involved in diagnosis and treatment, and people and their partners with lived experience of adenomyosis. The core component of the process was a 2-step modified Delphi electronic survey. The Steering Committee analysed the results and created the final core outcome set (COS) in a semi-structured meeting. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 241 outcomes was identified and distilled into a 'long list' of 71 potential outcomes. The final COS comprises 24 specific and 26 generic core outcomes across nine domains, including pain, uterine bleeding, reproductive outcomes, haematology, urinary system, life impact, delivery of care, adverse events and reporting items, all with definitions provided by the Steering Committee. Nineteen of these outcomes will apply only to certain study types. Although not included in the COS, the Steering Committee recommended that three health economic outcomes should be recorded. LIMITATIONS, REASONS FOR CAUTION: Patients from continents other than Europe were under-represented in this survey. A lack of translation of the survey might have limited the active participation of people in non-English speaking countries. Only 58% of participants returned to round two, but analysis did not indicate attrition bias. There is a significant lack of scientific evidence regarding which symptoms are caused by adenomyosis and when they are related to other co-existent disorders such as endometriosis. As future research provides more clarity, the appropriate review and revision of the COS will be necessary. WIDER IMPLICATIONS OF THE FINDINGS: Implementing this COS in future studies on the treatment of adenomyosis will improve the quality of reporting and aid evidence synthesis. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was received for this work. T.T. received a grant (grant number 2020083) from the South Eastern Norwegian Health Authority during the course of this work. T.T. receives personal fees from General Electrics and Medtronic for lectures on ultrasound. E.R.L. is the chairman of the Norwegian Endometriosis Association. M.G.M. is a consultant for Abbvie Inc and Myovant, receives research funding from AbbVie and is Chair of the Women's Health Research Collaborative. S.-W.G. is a board member of the Asian Society of Endometriosis and Adenomyosis, on the scientific advisory board of the endometriosis foundation of America, previous congress chair for the World Endometriosis Society, for none of which he received personal fees. E.S. received outside of this work grants for two multicentre trials on endometriosis from the National Institute for Health Research UK, the Rosetrees Trust, and the Barts and the London Charity, he is a member of the Medicines and Healthcare Products Regulatory Agency (MHRA), Medicines for Women's Health Expert Advisory Group, he is an ambassador for the World Endometriosis Society, and he received personal fees for lectures from Hologic, Olympus, Medtronic, Johnson & Johnson, Intuitive and Karl Storz. M.H. is member of the British Society for Gynaecological Endoscopy subcommittee. No other conflict of interest was declared. TRIAL REGISTRATION NUMBER: N/A.

A comparison of maternal calcium and magnesium levels in pre-eclamptic and normotensive pregnancies: an observational case-control study.

OBJECTIVE: Supplementing pregnant women at high risk of developing pre-eclampsia with calcium may reduce the incidence of the disease. This study examines differences in serum and hair concentrations of calcium and magnesium between women with pre-eclamptic and normotensive pregnancies. DESIGN: Observational case-control study. SETTING: Two teaching hospitals in Cape Town, South Africa. POPULATION: Women with pre-eclamptic (N = 96) or normotensive (N = 96) pregnancies, who delivered a single, live infant. METHODS: Demographic and current pregnancy details were retrieved from clinical notes. Each participant completed a dietary questionnaire. Venous blood samples were taken from each participant to assess serum calcium and magnesium concentrations. Hair samples were obtained from all participants and calcium and magnesium levels were measured by inductively coupled plasma optical emission spectrometry (ICPOES). MAIN OUTCOME MEASURE: Hair and serum calcium and magnesium concentrations were compared between women with pre-eclamptic and normotensive pregnancies. RESULTS: Diet and socio-economic status in the two groups were similar. There was no significant difference in the hair calcium level between women with pre-eclamptic [1241 parts per million (ppm); range, 331-4654 ppm] and normotensive (1146 ppm; range, 480-4136 ppm) pregnancies (P = 0.5). Hair calcium levels in both groups were not affected by HIV infection. CONCLUSION: Woman with pre-eclampsia showed no difference in chronic calcium status relative to normotensive women. This finding does not support the current belief that the mechanism by which calcium supplementation reduces the risk of developing pre-eclampsia is by correcting a nutritional deficiency.

A novel estrogen-free oral contraceptive pill for women: multicentre, double-blind, randomized controlled trial of mifepristone and progestogen-only pill (levonorgestrel).

BACKGROUND: The acceptability and continuation rate of oral contraceptive steroids are limited by unpredictable bleeding and the fear of long-term risks such as breast cancer. By inhibiting ovulation and by altering the receptivity of the endometrium, antagonists of progesterone, such as mifepristone, could be developed as estrogen-free novel contraceptives. METHODS: Multicentre, double-blind, randomized controlled trial comparing frequency of amenorrhoea (primary outcome), bleeding patterns, side effects and efficacy in women taking daily 5 mg mifepristone (n = 73) or 0.03 mg levonorgestrel (progestogen-only pill; POP, n = 23) for 24 weeks. RESULTS: More women were amenorrhoeic while taking mifepristone than POP (49 versus 0% P < 0.001), and fewer women bled or spotted for >5 days per month (4 versus 39% P < 0.001). Forty-eight percent of women who took mifepristone for 6 months had cystic glandular dilatation of the endometrium but none showed hyperplasia or atypia. There were no pregnancies in 356 months of exposure in women who used only mifepristone for contraception. Two pregnancies occurred in women taking mifepristone who were also using condoms for dual protection. CONCLUSIONS: Daily mifepristone (5 mg) is an effective oral contraceptive pill which has a better pattern of menstrual bleeding than an existing POP (levonorgestrel).

Psychological distress among women suffering from couple infertility in South Africa: a quantitative assessment.

BACKGROUND: Infertility in Africa is commonly associated with negative psycho-social consequences. To date, most studies from African countries addressing these consequences have been qualitative in nature. The aim of this study was to assess psychological distress quantitatively among women suffering from couple infertility in an urban community in South Africa. METHODS: The Symptom Checklist-90-R (SCL-90-R), a standardized instrument for the measurement of current psychological symptom status, was administered to 120 women at the time of their first presentation to an infertility clinic in a tertiary referral centre. The control group comprised 120 women presenting to local family planning clinics. In addition, socio-demographic information and data pertaining to the prevalence of abuse was captured through a structured questionnaire designed for the purpose of this study. RESULTS: Women suffering from involuntary childlessness scored significantly higher on all sub-scales and the global indices of distress of the SCL-90-R when compared to controls. In addition, women who reported abuse from their male partners had significantly higher scores on six of the 12 test scales when compared to infertile women in non-abusive relationships. CONCLUSIONS: Involuntary childlessness is associated with high levels of psychological distress. Women in abusive relationships are particularly at risk. This result is in keeping with several qualitative studies from African countries which describe infertility as an overwhelmingly negative and distressing experience. Cognizance needs to be taken of these experiences and effective interventions require medical, psychological and socio-cultural strategies.

'You are a man because you have children': experiences, reproductive health knowledge and treatment-seeking behaviour among men suffering from couple infertility in South Africa.

BACKGROUND: In Africa, infertility traditionally has been viewed as a female problem. This study explores reproductive health knowledge, health-seeking behaviour and experiences related to involuntary childlessness in men suffering from couple infertility. METHODS: Twenty-seven men from a diverse cultural urban community in South Africa participated in in-depth interviews at the time of their first visit to an infertility clinic in a tertiary referral centre. RESULTS: Men had little knowledge about the physiology of human fertility, causes of infertility and modern treatment options. Awareness of male factor infertility was, however, high. Most men appeared involved in the health-seeking process. Men described their emotional reactions to childlessness and the impact of infertility on marital stability, and many reported that infertile men suffered from stigmatization, verbal abuse and loss of social status. CONCLUSIONS: These findings improve our understanding of the reproductive health needs of men suffering from couple infertility in Africa. This understanding is essential for the effective integration of male partners into modern infertility management. The need for appropriate counselling of men and, most particularly, for education of the community is recognized.

Cyproterone acetate for hirsutism.

BACKGROUND: Hirsutism is a distressing and relatively common endocrine problem in women which may prove difficult to manage. Cyproterone acetate, an anti-androgen, is frequently used to treat hirsutism, usually in combination with ethinyl estradiol. OBJECTIVES: The objective of this review was to investigate the effectiveness of cyproterone acetate alone, or in combination with ethinyl estradiol, in reducing hair growth in women with hirsutism secondary to ovarian hyperandrogenism. SEARCH STRATEGY: The Cochrane Menstrual Disorders and Subfertility Group trials register was searched (last search - 4 June 2002). The Cochrane Menstrual Disorders and Subfertility Group register is based on regular searches of MEDLINE (1966 to 2002), EMBASE (1980 to 2002), CINAHL (1982 to 2002), PsycINFO (1987 to 2002) and CENTRAL (Issue 2, 2002 of the Cochrane Library) the handsearching of several journals and conference proceedings, and searches of several key grey literature sources. All publications of randomised controlled trials of cyproterone acetate with or without estrogen versus placebo or other drug therapies for hirsutism were identified. SELECTION CRITERIA: All randomised controlled studies comparing:- cyproterone acetate to placebo- cyproterone acetate with ethinyl estradiol to placebo- cyproterone acetate with ethinyl estradiol to cyproterone acetate alone- cyproterone acetate (with or without estradiol) to other medical therapies for treatment of hirsutism. DATA COLLECTION AND ANALYSIS: Eleven studies were identified which fulfilled the inclusion criteria. Nine randomised studies were included in the review, and two were excluded because of insufficient information. Only one study had more than 100 women included in the analysis. The major outcomes included: subjective improvement in hirsutism, changes in Ferriman Gallwey scores, changes in linear hair growth and hair shaft diameter, alterations in endocrine parameters, side effects to treatment, withdrawals during therapy MAIN RESULTS: There were no clinical trials comparing cyproterone acetate alone with placebo. There was one small study comparing cyproterone acetate in combination with ethinyl estradiol to placebo. In this study there was a significant subjective reduction in hair growth with cyproterone acetate therapy, although the confidence limits were large. There were no studies comparing cyproterone acetate alone with cyproterone acetate in combination with ethinyl estradiol to treat hirsutism. In studies where cyproterone acetate was compared to other drug modalities (ketoconazole, spironolactone, flutamide, finasteride, GnRH analogues) no difference in clinical outcome was noted. There were, however, endocrinological differences in androgen and estrogen levels between different drug therapies. There were insufficient data to assess differences in side effects between women treated with cyproterone acetate and other medical therapy. REVIEWER'S CONCLUSIONS: Cyproterone acetate combined with estradiol results in a subjective improvement in hirsutism compared to placebo. Clinical differences in outcome between cyproterone acetate and other medical therapies were not demonstrated in the studies included in this review. This may be because of the small size of the studies, lack of standardized assessment and lack of objective determinants of improvement in hirsutism. The endocrinological effects of the different drug therapies reflect the mode of action. Larger carefully designed studies are needed to compare efficacy and safety profiles between drug therapies for hirsutism.

Amenorrhea associated with contraception-an international study on acceptability.

Surveys undertaken in the 1970s and 1980s suggested that amenorrhea was unacceptable to most women, especially in developing countries. More recent research suggests that increasing numbers of women in the developed world prefer to menstruate less often. In a questionnaire survey of 1001 women attending family-planning clinics and 290 contraceptive providers in China, South Africa, Nigeria and Scotland, only among black women in Africa did the majority like having periods. In all other groups, most women disliked periods, which were "inconvenient" and associated with menstrual problems. Given the choice, the majority of Nigerian women would prefer to bleed monthly. Elsewhere, women would opt to bleed only once every 3 months, or not at all. In all except the Chinese centers, the majority of women would be willing to try a contraceptive which induced amenorrhea. Providers tended to overestimate the importance of regular menstruation to their clients. This is an important observation for scientists and funding agencies involved in developing new methods of contraception.

Investigation of hormonal male contraception in African men: suppression of spermatogenesis by oral desogestrel with depot testosterone.

BACKGROUND: Suppression of spermatogenesis to azoospermia is required for effective hormonal male contraception, but the degree of suppression varies between ethnic groups. We here report the first study of hormonal suppression of spermatogenesis in two African centres using a regimen of oral progestogen with depot testosterone. METHODS A total of 31 healthy men (21 black) were recruited in Cape Town and 21 men in Sagamu, Nigeria. Subjects were randomized to take either 150 or 300 micro g desogestrel daily p.o. with testosterone pellets. In Cape Town, desogestrel was administered for 24 weeks with 400 mg testosterone re-administered 12 weekly. In Sagamu, desogestrel was administered for 52 weeks with 200 mg testosterone (later increased to 400 mg) re-administered 12-weekly. RESULTS: In Cape Town, 22 men completed at least 20 weeks treatment. Azoospermia was achieved in 8/10 and 8/12 men in the 150 micro g and 300 micro g desogestrel groups. Four men in Sagamu withdrew. Azoospermia was achieved in all 17 men in the two groups. There were no significant changes in lipoprotein or haemoglobin concentrations in any group. CONCLUSION: These data demonstrate that the combination of oral desogestrel with depot testosterone is an effective regimen for suppression of spermatogenesis in African as in Caucasian and Chinese men, with azoospermia achieved in a total of 83/98 (85%) men.

Inhibition of progesterone secretion with trilostane for mid-trimester termination of pregnancy: randomized controlled trials.

BACKGROUND: Progesterone is central to the maintenance of pregnancy, and is thus the ideal target for fertility regulation. Two mechanisms by which progesterone can be targeted are: receptor blockade and reduction of progesterone production through enzyme inhibition. Mifepristone, a receptor blocker, is usually given as 'pretreatment' prior to prostaglandin administration in mid-trimester termination of pregnancy (TOP). Unfortunately, there are difficulties accessing mifepristone in developing countries, and TOP is therefore performed using prostaglandins alone, which results in unacceptably long induction-to-abortion intervals. Trilostane is a 3beta-hydroxysteroid dehydrogenase inhibitor which reduces progesterone production. In these mid-trimester studies it is evaluated as a method of pretreatment prior to misoprostol administration. METHODS: Three consecutive randomized controlled trials comparing different trilostane regimens for pretreatment were performed. In study 1, trilostane was compared with placebo; in study 2, two doses of trilostane were compared (1080 mg and 720 mg); in study 3, the effect of adding danazol to trilostane as combination therapy was evaluated. The primary outcome in all the studies was the induction-to-abortion interval. Serum progesterone, estradiol and cortisol were measured serially during treatment. RESULTS: In study 1, 48 women were randomized. The median induction-to-abortion interval was 9 h in the trilostane group and 18.5 h in the placebo group (P < 0.0001). Progesterone and estradiol production was significantly reduced in the women receiving trilostane, with maintenance of diurnal cortisol variation. Twenty-eight women were randomized in study 2, which demonstrated that there was no significant difference in the induction-to-abortion interval using 1080 mg and 720 mg trilostane when compared with the higher doses used in study 1. Study 3, in which 40 women were included, failed to show any additional benefit using combination therapy with danazol and trilostane. CONCLUSIONS: Trilostane is an effective pretreatment agent in mid-trimester TOP.

Infertility in South Africa: women's reproductive health knowledge and treatment-seeking behaviour for involuntary childlessness.

BACKGROUND: Infertility is a major reproductive health problem in Africa. This paper presents the findings of two studies which focus on the knowledge that infertile women have about fertility and the causes of infertility, their treatment-seeking behaviour and their expectations of an infertility clinic. METHODS: A total of 150 infertile women from a culturally diverse, urban community in South Africa participated in the two studies. Both qualitative and quantitative research methods were applied using in-depth, semi-structured interviews and structured questionnaires. RESULTS: The women who participated had little knowledge about human reproduction and modern treatment options for infertility. They were highly motivated to find treatment and accessed both traditional and modern health care. Treatment barriers within modern health care were identified. CONCLUSIONS: The importance of health education and counselling is recognized, and both need to be integrated into infertility management, particularly in the developing world. The introduction of clinical guidelines is recommended in order to overcome treatment barriers and improve the delivery of health services.

'Men leave me as I cannot have children': women's experiences with involuntary childlessness.

BACKGROUND: This study explores the concerns and experiences related to involuntary childlessness of infertile women living in a diverse cultural urban community in South Africa. METHODS: In-depth interviews were conducted with 30 women seeking treatment for involuntary childlessness. Women were interviewed at the time of their first visit to an infertility clinic in a tertiary referral centre. RESULTS: All women verbalized intense emotions about their involuntary childlessness. In addition, a large number of women experienced negative social consequences including marital instability, stigmatization and abuse. CONCLUSIONS: These findings demonstrate that infertility can have a serious effect on both the psychological well-being and the social status of women in the developing world. Furthermore, the study provides insight into the cultural context of involuntary infertility in South Africa. The delivery of good infertility care in a community requires awareness of the implications of infertility and insight into the context in which these occur. Since many of the negative social implications of infertility are probably rooted in low status women in the developing world, effective intervention will ultimately require social, economical and political changes.

Is postpartum contraceptive advice given antenatally of value?

In response to the concept that a good postpartum program should begin prenatally, this study was designed to determine whether the provision of expert contraceptive counseling during the antenatal period would have an impact on contraceptive uptake, patterns of contraceptive usage, and pregnancy rates during the first year after childbirth. Over 500 women attending antenatal clinics in each of three centers (Edinburgh, Scotland; Shanghai, People's Republic of China; Cape Town, South Africa) were randomized to receive expert contraceptive advice (participants, n = 771) or the standard advice routinely given in that setting (controls, n = 866). Follow-up was by postal or interviewer-administered questionnaires at 16 and 52 weeks after childbirth. There were no significant differences in the prevalence of contraceptive use at one year (over 79% in all centers) between participants and controls. In Edinburgh, participants were more likely to undergo sterilization (p < 0.01) than controls, otherwise there were no differences among Edinburgh, Shanghai, or Cape Town in either the methods of contraception chosen or in the methods used over time. Contraceptive counseling delivered antenatally appeared to have no impact on the pregnancy rate during the first year after childbirth. In Shanghai, over 11% of women in both groups underwent termination of pregnancy in the year of follow-up. In conclusion, although women in all centers said they found the opportunity to discuss contraception antenatally was useful, it had very little effect on contraceptive use or on subsequent pregnancy rates.

Endocrine function in HIV-infected women.

Infection with the human immunodeficiency virus (HIV) results in a chronic systemic illness with multi-organ involvement, severe immunosuppression and profound cachexia. It has had a major impact on women's health. Endocrine abnormalities may contribute to the clinical presentation and therefore appropriate treatment would theoretically improve the patient's condition. This pilot study was undertaken to assess the endocrine status in a group of HIV seropositive women with the view to developing recommendations for future investigations. Thirteen women were recruited from a clinic for HIV-infected patients. All women had a comprehensive general and gynecological examination. Basal endocrine status was assessed and combined pituitary testing with gonadotropin-releasing hormone, thyrotropin-releasing hormone, growth hormone-releasing hormone and corticotropin-releasing hormone was performed. None of the participating women presented with gynecological complaints or had symptoms suggestive of an endocrinopathy. On questioning, seven women complained of menstrual abnormalities. Three had a body mass index of less than 20 kg/m2. Genital tract infections were common. Endocrine assessment demonstrated abnormalities of the pituitary-adrenal, pituitary-thyroid and pituitary-ovarian axes in seven women. One woman had panhypopituitarism. In six of the seven affected women CD4 counts were below 200 cells/mm3. Alterations in endocrine function were observed in seven of the women tested. While routine endocrine testing may not be indicated in all HIV-seropositive women, we should be aware of possible subtle presentations of endocrine abnormalities which may require treatment, especially in stress situations.

Antibodies to Chlamydia trachomatis in patients presenting with ectopic pregnancy at Groote Schuur Hospital.

OBJECTIVES: To determine the prevalence of antibodies to Chlamydia trachomatis in women presenting with ectopic pregnancies to Groote Schuur Hospital. METHODS: C. trachomatis antibody titres were measured using a modified micro-immunofluorescence test in women presenting with ectopic pregnancy. Control subjects were drawn from women with term pregnancies and an uneventful reproductive history. RESULTS: Seventy-four patients and controls were studied. Demographic variables were controlled for at time of entry into the study. A significant association between the number of lifetime sexual partners and exposure to C. trachomatis was noted (P = 0.001). Patients with ectopic pregnancies had significantly higher antibody titres than control subjects (P = 0.001), and in both groups the prevalence of background antichlamydial antibody was high (ectopic pregnancies 59%, pregnant controls 32%). CONCLUSIONS: While the role of C. trachomatis infection in women who develop ectopic pregnancies needs to be explored further, it seems wise to treat them all with empirical antibiotics at the time of presentation.

Morphine suppresses the oxytocin response in breast-feeding women.

The activity of opiate-mediated regulatory mechanisms of oxytocin secretion during breast-feeding was studied by the administration of either morphine, naloxone or placebo to women prior to the commencement of breast-feeding. Seventeen healthy women in the first week after delivery who had established lactation were randomized to receive either intravenous morphine 5 mg (n = 6), naloxone 2.4 mg (n = 6) or a placebo, sterile water (n = 5), which was given prior to commencement of breast-feeding. Oxytocin levels were measured by radioimmunoassay prior to initiation of breast-feeding and then at 2-min intervals until the feed was complete. Breast-feeding produced a significant rise in oxytocin levels in the control and naloxone groups but no significant rise in the patients given morphine. There was a significant reduction in oxytocin response following morphine administration when compared to placebo but not between naloxone and placebo. In conclusion, oxytocin secretion to breast-feeding is inhibited by exogenous morphine when compared to a control group but the administration of naloxone did not produce a significant difference from control.

The effect of emotional support on maternal oxytocin levels in labouring women.

OBJECTIVE: The presence of a supportive companion to women in labour has been found to reduce the duration of labour and the incidence of oxytocin augmentation. The mechanism which produces this improvement is unknown but work in animals suggests that environmental disturbance produces changes in endogenous oxytocin secretion. This study was carried out to assess maternal oxytocin secretion in relation to the presence of a supportive companion in labour. STUDY DESIGN: A randomised controlled trial involving allocation of unsupported women in the first stage of labour to a period of 1 h with a supportive companion or 1 h without. Sixteen women with uncomplicated singleton pregnancies who were in the active phase of the first stage of labour were studied. Maternal oxytocin levels were assayed by radioimmunoassay for 16 min (eight specimens) before and after the support or control period. RESULTS: There are no differences between maternal oxytocin levels in the two groups of patients. There was no difference in either of the two groups between the oxytocin levels pre and post the support/control period. CONCLUSIONS: One hour of birth support in the first stage of labour did not improve maternal oxytocin levels when compared to a control group.

Effects of morphine administration on the fetal production of oxytocin in labour.

1. Animal and human work has indicated that maternal oxytocin secretion is under the control of endogenous opiates. Previous workers have described the fetal production of oxytocin in addition to maternal production. The study of the interaction between exogenously administered opiates and oxytocin secretion may give insight into the activity of any opiate-mediated regulatory mechanism of oxytocin secretion in the fetus. This study was designed to investigate the effect of an opiate (5 mg of morphine) given to the mother on the fetal production of oxytocin in labour. 2. Morphine was given by the attending clinicians for analgesic purposes to women in the first stage of labour. After delivery umbilical artery vein and maternal vein specimens were taken. 3. Four groups of patients were studied: women after normal vaginal delivery without analgesia in labour (n=10); women after normal vaginal delivery who had morphine administration in the first stage of labour (n=12); women who had an emergency Caesarean section in the first stage of labour (n=11); women who had an elective Caesarean section at term who were not in labour (n=11). 4. Oxytocin levels were measured by radioimmunoassay in the maternal vein, umbilical artery and umbilical vein specimens. Morphine was measured by radioimmunoassay in the umbilical vein specimens. 5. The umbilical artery minus vein concentration of oxytocin was calculated for each patient (A-V). There was no change in the umbilical (A-V) concentration of oxytocin if morphine had been given to the mother in labour; this applied to fetuses delivered vaginally or by Caesarean section. When the fetuses who were exposed to morphine were analysed separately, there was no correlation between the umbilical vein morphine concentration and the umbilical (A-V) oxytocin concentration either in Caesarean or vaginal deliveries. 6. Fetal oxytocin production was not affected by the maternal administration of morphine in the first stage of labour. This applies to the oxytocin production in the first and second stage of labour.

The 24-hour rhythm of oxytocin and beta-endorphin secretion in human pregnancy.

OBJECTIVE: Animal work suggests that maternal oxytocin secretion is influenced by the secretion of endogenous opioids in pregnancy. Spontaneous labour and pre-labour uterine activity follow a 24-hour rhythm the origin of which has not been explained but may be related to diurnal changes in oxytocin secretion. This study was performed to document the changes over a 24-hour period in maternal oxytocin and beta-endorphin secretion. DESIGN: A 4-hourly blood profile was undertaken for a 24-hour period. PATIENTS: Sixteen women with singleton pregnancies of more than 36 weeks gestation and 10 women with pregnancies in the mid trimester were studied. MEASUREMENTS: Blood was sampled 4-hourly for 24 hours beginning at 1200 h. Oxytocin was measured in all patients and beta-endorphin-like immunoreactivity was measured in 15 patients. RESULTS: A simple index was defined for comparing night-time levels to daytime levels for both oxytocin and beta-endorphin. In all cases more than 36 weeks gestation the index was positive for oxytocin (night-time levels were higher) and in all cases the index was negative for beta-endorphin (night-time levels were lower). In the mid trimester women all values of the index for oxytocin were positive but in the beta-endorphin group equal numbers demonstrated a positive or a negative index. CONCLUSIONS: Reciprocal 24-hour rhythms were demonstrated between oxytocin and beta-endorphin; however, it is not clear whether this relationship is causal.

Laparoscopically assisted vaginal hysterectomy (LAVH)--an alternative to total abdominal hysterectomy.

OBJECTIVE: To assess the feasibility of performing laparoscopically assisted vaginal hysterectomy (LAVH) on women referred for total abdominal hysterectomy (TAH). DESIGN: Prospective intervention study on women referred for TAH from a gynaecological outpatient clinic. SETTING: Groote Schuur Hospital, Cape Town. This institution accepts patient referrals from community hospitals and family physicians for hospitalised care. PATIENTS: Forty-one consecutive women referred for TAH were suitable for LAVH. Women able to undergo conventional vaginal hysterectomy, women with uterine fibroids exceeding 14 weeks in size and subjects with malignant disease were excluded. The most common indication for hysterectomy was persistent abnormal bleeding. INTERVENTION: Of the 41 women assessed pre-operatively as suitable for LAVH, the procedure was successfully performed in 40 by means of a bipolar desiccation and scissors transection technique with re-usable equipment. MAIN OUTCOME MEASURES: Assessment of intra-operative and postoperative morbidity, surgical complications, operating time, length of hospitalisation and assessment at postoperative visit 6 weeks after surgery. RESULTS: Only 1 woman was unable to undergo successful LAVH because she had pelvic adhesions and densely adherent loops of bowel; a TAH was performed. No operative complication occurred. One woman had postoperative vaginal bleeding controlled with a vaginal pack, and a diagnosis of von Willebrand's disease was subsequently established. No patient had febrile morbidity and when reviewed at clinic 6 weeks later all women were well. CONCLUSIONS: LAVH is possible in many women in whom hysterectomy is indicated but conventional vaginal hysterectomy is not feasible. In this study LAVH was found to be a safe procedure with minimal complications.

Laparoscopic findings in women with chronic pelvic pain.

OBJECTIVE: This study was undertaken to assess the spectrum of pelvic pathology observed at laparoscopy in women with chronic pelvic pain, and to compare women with an identifiable cause of pain to those with no visible pelvic pathology, with regard to symptomatology and demography. DESIGN: Retrospective case control study reviewing laparoscopy reports and patient records. SETTING: Department of Obstetrics and Gynaecology, Groote Schuur Hospital. PATIENTS: One hundred and thirty-six consecutive women undergoing laparoscopic assessment for undiagnosed pelvic pain of at least 6 months' duration, between 1989 and 1991. MAIN OUTCOME MEASURES: The presence of endometriosis, pelvic adhesions, other pelvic pathology and 'negative' laparoscopic findings was assessed. The association between pelvic pathology and specific symptomatology, fertility, contraceptive use, past pelvic surgery, ethnic group and smoking is examined. RESULTS: No cause of pain was identified at laparoscopy in 30% of these patients, while endometriosis was found in 16% of women and pelvic adhesions in 40%. The 41 women with no identifiable laparoscopic abnormality did not differ significantly from the 95 with pelvic abnormalities in respect of age, parity, duration of pain, frequency of dysmenorrhoea and dyspareunia or the presence of gastro-intestinal or urinary symptoms. However, injectable hormonal contraception use was more common in the group with negative laparoscopic findings and smoking was more common among the women with pelvic pathology. CONCLUSION: Chronic pelvic pain with a laparoscopically normal pelvis is a common problem in Cape Town, occurring with a frequency similar to that reported from various overseas centres. Women with this problem are not readily identified by demographic profile or symptom complex.