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Objectives Our purpose was to review all the major complications of laparoscopy in 6500 consecutive laparoscopies from one centre. We also felt it was important to conduct this study because of the current debate on the use of the Veress needle or the Hasson cannula. Design All the major complications from laparoscopies performed from June 1 1991 to March 31 1995 were documented. This is the largest series from one centre. Each laparoscopy was registered on computer. A distinction between operative and diagnostic laparoscopies was not made by the computer. Results A major complication was defined as one that required laparotomy. In this series eight major complications were recorded. The incidence of major complications was 1.23 per 1000. No vascular injury occurred as a result of using a Veress needle or closed trocar entry. Conclusion Despite advances in operative and diagnostic laparoscopy, complications still occur. From this study there is currently no evidence to suggest that the Veress needle should be banned in favour of the open Hasson technique. The gynaecologist, anaesthetist and consumer need to be aware of the complication rates for gynaecological day surgery laparoscopy.

Buserelin acetate, a luteinizing hormone-releasing hormone agonist, is known to be effective in the shrinkage of uterine fibroids. A prospective trial was undertaken (1) to compare the efficacy of intranasal (IN) and subcutaneous (SC) administration of buserelin acetate and (2) to assess if tumor regression correlated with fibroid size and/or patient age. Forty patients were randomly allocated to receive 6 months of either IN buserelin acetate (n = 21) or SC buserelin acetate (n = 19). Four patients did not complete the study and were excluded from statistical analysis. Fibroid regression occurred in all 36 patients. Overall regression to 66% or less of the initial fibroid volume occurred in 70% of subjects. There was no significant difference in fibroid shrinkage between the two administration routes. A significant positive correlation was found between initial fibroid size and subsequent fibroid regression, with larger tumors being more likely to shrink than smaller fibroids. No correlation was found between the patient's age and the extent of fibroid regression.

Ovulation induction using clomiphene citrate, gonadotropins, and gonadotropin-releasing hormone is reviewed. The short- and long-term consequences of these therapies are discussed in detail.

Objective: We have previously reported on the point prevalence of ovarian lesions detected by transvaginal ultrasound (TVU) in 515 asymptomatic women at least 5 years postmenopause. The aims of this study were to report, in the same women, on the repeatability of visualization of the ovaries (TVU) and the natural history of ovarian lesions seen at baseline but not treated surgically and to assess whether any women developed new ovarian abnormalities 12 months later. Method(s): The study involved a cohort of 515 postmenopausal women recruited from the community, at least 5 years past their last period. They were assessed at baseline and again after 12 months with TVU and serum levels of inhibin and CA-125. Result(s): The right and left ovaries were seen on both occasions in 80% and 68% of women, respectively. Of the 49 women who had an ovarian lesion at baseline, did not undergo surgery at that time, and had a follow-up TVU, the lesion was unchanged 12 months later in 30 women. Four women developed a new ovarian lesion within the 12 months. None of the 14 women who underwent surgery on the basis of the ovarian appearance at baseline, or the 2 who had surgery on the basis of the ovarian appearance at follow-up, had an ovarian malignancy. Conclusion(s): The use of TVU in women at least 5 years after menopause is problematic because the ovaries cannot be visualized in all women and because TVU has the potential to identify many benign lesions that would otherwise remain undetected. These are important considerations in weighing up the risks and benefits of using TVU as a screening tool. © 2009 by The North American Menopause Society.

Objective(s). Granulosa cell tumors (GCT) and mucinous cystadenocarcinoma of the ovary are associated with elevated circulating levels of immunoreactive inhibin. Measurement of serum inhibin levels provides a useful tumor marker in the management of ovarian tumors. Inhibin is a dimeric ovarian glycoprotein hormone consisting of one alpha and one of two beta subunits. The beta subunits can dimerize to form activin. Activin is bound and its action modulated by another gonadal peptide, follistatin. In this study the patterns of expression of the three inhibin subunit genes, the follistatin gene, and the activin receptor type II gene have been determined. Methods. Gene expression was analyzed in RNA prepared from 16 primary ovarian tumors using reverse transcriptase-polymerase chain reaction (RT-PCR). Gene- specific primes were used for RT-PCR; the products were analyzed by Southern blot analysis with gene-specific riP-labeled probes. Results. Widespread expression of these genes was found in all of the tumor types examined. Abundant expression of the inhibin alpha subunit gene was observed in the GCT and to a lesser extent in the mucinous and serous tumors. beta subunit expression was also present in the GCT and to a lesser extent in the other tumors. Widespread expression of both the activin receptor type II and the follistatin genes was also observed. Conclusions. Expression of the inhibin subunit genes in GCT and some epithelial tumors confirms that these tumors are the source of the increased immunoreactive inhibin seen in the circulation of patients with ovarian tumors. Expression of the activin receptor type II and follistatin genes suggests a paracrine role for activin in these tumors which may be modulated by follistatin, particularly in the GCT.

Excessive endometrial angiogenesis is proposed as an important mechanism in the pathogenesis of endometriosis. Evidence is reviewed for the hypothesis that the endometrium of women with endometriosis has an increased capacity to proliferate, implant and grow in the peritoneal cavity. Data is summarized indicating that the endometrium of patients with endometriosis shows enhanced endothelial cell proliferation. Results are also reviewed indicating that the cell adhesion molecule integrin alpha(v)beta3 is expressed in more blood vessels in the endometrium of women with endometriosis when compared with normal women. Taken together, these results provide evidence for increased endometrial angiogenesis in women with endometriosis when compared with normal subjects. Endometriosis is one of the family of angiogenic diseases. Other angiogenic diseases include solid tumours, rheumatoid arthritis, psoriasis and diabetic retanopathy. Excessive endometrial angiogenesis suggests novel new medical treatments for endometriosis aimed at the inhibition of angiogenesis.

Background. Inhibin is an ovarian hormone that inhibits the secretion of follicle-stimulating hormone (FSH) by the anterior pituitary gland. Women with granulosa-cell tumors of the ovary have elevated serum inhibin concentrations, but whether the concentrations are increased in women with other ovarian tumors is unknown. Methods. We measured serum inhibin and FSH concentrations before surgery in 212 postmenopausal women with suspected ovarian cancer and after surgery in 210 of them. Results. Eighteen of the 22 women (82 percent) with mucinous carcinomas (mucinous cystadenocarcinomas and mucinous borderline cystic tumors) of the ovary had elevated serum inhibin concentrations, whereas only 9 of the 53 women (17 percent) with serous carcinomas (serous cystadenocarcinomas and serous borderline cystic tumors) had elevated levels. Serum inhibin concentrations were also elevated in 2 of 12 women (17 percent) with clear-cell carcinomas, 4 of 26 women (15 percent) with undifferentiated carcinomas, 3 of 3 women (100 percent) with granulosa- cell tumors, and 5 of 27 women (19 percent) with other ovarian cancers. The serum concentrations of inhibin were increased in 2 of 28 women (7 percent) with nonovarian pelvic cancers and 11 of 41 women (27 percent) with benign ovarian diseases. All women but one with initially elevated serum inhibin concentrations had low values one week after surgery. Serum inhibin concentrations correlated negatively with serum FSH concentrations (P = 0.05) in women with granulosa-cell tumors but not in women with other tumors, suggesting that the inhibin secreted by tumors in the latter group has decreased biologic activity. Conclusions. Serum inhibin concentrations are elevated in most postmenopausal women with mucinous carcinomas of the ovary and in some women with other types of epithelial ovarian tumors. The concentrations fall after tumor removal.

We investigated the role of vascular endothelial growth factor (VEGF) in ovarian hyperstimulation syndrome (OHSS). Two similar peaks of permeability activity were seen in OHSS ascites and liver ascites spiked with recombinant human VEGF (rhVEGF); no activity was seen in control liver ascites. Incubation with rhVEGF antiserum decreased activity in the two OHSS peaks by 79% and 65% and the two spiked liver peaks by 49% and 50%. Control serum produced 24% and 27%, and 17% and 0% reductions, respectively. This is evidence that the major capillary permeability agent in OHSS ascites fluid is VEGF.

Objective: The purpose of this pilot study was to develop an assessment instrument to evaluate the level of skill of laparoscopic surgeons with regard to operative laparoscopy. Subjects: A total of 16 doctors working in obstetrics and gynaecology were tested on the Monash University gynaecological laparoscopic pelvi-trainer. Eight candidates were consultants with 9-28 years of practice in operative laparoscopy, and eight were registrars with up to 6 years of practice in operative laparoscopy. Six consultants and one registrar were from rural Australia. Design(s): Subjects were asked to complete 10 laparoscopic tasks. Nine of these were designed to test manual dexterity skills and the correct use of laparoscopic instruments. One task tested theoretical knowledge of electrosurgery by means of four short-answer questions. Candidates were marked on the basis of precision and speed. Heart rate measurements were taken 20 min prior to the test, at 5-min intervals, and at the start and end of each task thereafter. Result(s): The highest pass rate (81.25%) was recorded for task 1, i.e. setting up the endoscopic visualization system. The median time to complete this task was 168 s. No candidate could repair a severed ovarian ligament with an intracorporeal knot within 5 min. No candidate could successfully answer all four electrosurgery questions. Conclusion(s): It is possible to objectively evaluate basic operative skills of laparoscopists by means of well-structured tasks and marking criteria.

Background and objective. We have previously reported elevated serum immunoreactive inhibin (INH) levels in patients with ovarian malignancies, particularly granulosa cell and mucinous tumours. The present study was designed to compare INH measurements using a heterologous radioimmunoassay with cross-reactivity for inhibin alpha-subunit derived peptides with measurements obtained using a new ELISA specific for dimeric inhibin-A. It was hypothesized that granulosa cell tumours may secrete significant quantities of inhibin-A whereas mucinous tumours were unlikely to do so because of the lack of a relation between INH and FSH measurements in the latter group. Design. Serum samples obtained from women found to have ovarian cancer were assayed using the heterologous radioimmunoassay (the Monash assay) and using an ELISA specific for dimeric inhibin (the Groome assay) and the results were compared. Patients. Samples for assay were available from 69 normal post-menopausal control women, 12 patients with mucinous tumours of the ovary, 26 with serous tumours, 7 with granulosa cell tumours and 8 with various other ovarian tumours. Patients were post-menopausal or had been subjected to bilateral oophorectomy at the time these samples were collected. Measurements. The Monash and Groome assays were carried out as described previously. The upper limit of normal for post-menopausal women in the Monash assay was 122 U/l and for the Grooms assay was calculated to be 32 ng/l. Results. Among the 69 normal subjects, 4 were found to have elevated inhibin levels using the Monash RIA (133-190 U/l) and 4 were found to have elevated levels in the Groome ELISA (45.5-55.3 ng/l). Among 12 patients with mucinous tumours, 10 (83%) had elevated inhibin levels using the Monash assay but only 3 (25%) had elevated levels with the Groome assay (P < 0.005). Among 26 with serous tumours, 15 (58%) had elevated levels in the Monash assay but only 1 (4%) in the Groome assay (P < 0.001). Among 7 samples fr

Ovulation induction by means of the pulsatile subcutaneous administration of gonadotrophin-releasing hormone by way of an infusion pump is described. The clinical outcome in 50 courses of treatment, which totalled 116 treatment cycles, was analysed and was compared with the pregnancy rates that were obtained with the administration of human pituitary gonadotrophins. We found that the pregnancy rates for these two treatments were similar. We also have shown that for those women who ovulated as a result of such treatment the conception rates were similar to those in ovulatory women who had discontinued contraception. We conclude that gonadotrophin-releasing hormone has an important place among the ovulation-induction agents.

Whereas the dose of hMG is significantly correlated with both BMI and BW, commencing the more obese patient on higher hMG doses is not justified in view of the cancellation of cycles from over-responsiveness in the more obese patients started on higher hMG dosage regimens. If the more obese patient is slow to respond, however, a greater degree of clinical freedom may be exercised to increase the dose. The ultimate outcome of the cycle is not related to BMI, BW, or the dose of hMG used.

A single cause for the development of endometriosis is unknown. Of the historical hypotheses for the development of endometriosis, coelomic metaplasia and transplantation of retrograde endometrium have been the most widely accepted. Of the modern factors, which appear significant in the subsequent development of endometriosis, genetic predisposition and disturbed angiogenesis are the most intriguing. Active studies are in progress to attempt to identify genes relevant to the development of endometriosis. Active research is also studying the vascular supply to areas of endometriosis and the role of angiogenesis, or new blood vessel formation? in the pathogenesis of this disease. The availability of molecular biology probes, as well as medicines, which inhibit angiogenesis are direct consequences of the application of this basic research to this common clinical problem.

Objective: To compare the proliferation of endothelial, epithelial, and stromal cells in the endometrium of women with endometriosis and normal controls. Design(s): Proliferating cells were identified using the monoclonal antibody antiproliferating cell nuclear antigen. A second antibody (CD34) was used to identify endothelial cells (ECs). Setting(s): University Department of Obstetrics and Gynaecology. Patient(s): Women with laparoscopically proven endometriosis, n = 30. Controls were women with a normal pelvis at laparoscopy performed for tubal sterilization or for infertility due to a male factor, n = 27. Main Outcome Measure(s): Endothelial cells: proliferative index. Epithelial and stromal cells: semi-quantitative immunostaining score. Result(s): The mean EC proliferative index was significantly greater in those with endometriosis compared with controls. This difference was most marked during the proliferative phase of the menstrual cycle. Proliferative phase epithelial and stromal cells demonstrated significantly higher immunostaining scores in endometriosis patients than in controls. Conclusion(s): We have demonstrated increased numbers of proliferating ECs as well as epithelial and stromal cells in proliferative phase endometrium of women with endometriosis. This suggests that the endometrium of these women might have an enhanced ability to implant and survive in ectopic locations.

Objective: The purpose of this study was to assess the level of skill of laparoscopic surgeons in electrosurgery. Design(s): Subjects were asked to complete a practical diathermy station and a written test of electrosurgical knowledge. Setting(s): Tests were held in teaching and non-teaching hospitals. Sample: Twenty specialists in obstetrics and gynaecology were randomly selected and tested on the Monash University gynaecological laparoscopic pelvi-trainer. Twelve candidates were consultants with 9-28 years of practice in operative laparoscopy, and 8 were registrars with up to six years of practice in operative laparoscopy. Seven consultants and one registrar were from rural Australia, and three consultants were from New Zealand. Method(s): Candidates were marked with checklist criteria resulting in a pass/fail score, as well as a weighted scoring system. We retested 11 candidates one year later with the same stations. Main Outcome Measure(s): No improvement in electrosurgery skill in one year of obstetric and gynaecological practice. Result(s): No candidate successfully completed the written electrosurgery station in the initial test. A slight improvement in the pass rate to 18% was observed in the second test. The pass rate of the diathermy station dropped from 50% to 36% in the second test. Conclusion(s): The study found ignorance of electrosurgery/diathermy among gynaecological surgeons. One year later, skills were no better.

Inhibin was first isolated in 1985. Major progress has been made in defining various aspects of its structure and physiology, using a heterologous radioimmunoassay. Current research is aimed at characterizing the nature of the circulating forms of inhibin and is examining whether there are sex-specific roles for inhibins A and B. It has been recognized that various forms of epithelial and stromal ovarian cancer produce members of the inhibin peptide family but the precise nature of these products is not yet clear. The recognition that the inhibin subunits together with follistatin are expressed locally within the pituitary has lead to an investigation of their possible roles in intrapituitary regulation. It is clear that these peptides also have intragonadal roles. Of particular current interest is the nature of the signals that control the specificity of cellular peptide production and that determine whether a particular cell produces inhibin or activin. The inhibins are members of a complex family with many potential roles in physiology and pathophysiology. The role of the inhibins in feedback control of follicle stimulating hormone in the male, particularly, remains unclear. New applications for inhibin and related peptides are likely to be developed.

Reproductive medicine encompasses a variety of disorders resulting from disturbed gonadal function. Such disorders affect all age groups, and their rational therapy depends on comprehensive understanding of the physiology of the hypothalamo-pituitary-gonadal axis and of the pathophysiological disturbances which may occur. In a deliberately selective manner, this review has highlighted Australian contributions which include: new knowledge of the physiology of inhibin; approaches to the management of male infertility; the use of gonadotrophins and gonadotrophin releasing hormone in ovulation induction; new advances in our understanding of the pathophysiology and management of the polycystic ovarian syndrome; the use of superactive GnRH agonists in the management of disorders such as uterine fibroids and also the use of parenteral estradiol and testosterone replacement in women suffering from sexual dysfunction at the menopause. The contributions of Australian medicine have been significant.

Fibroids (leiomyomata) are the most common tumors in women, but their etiology is unknown. The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) may be important in the growth of these benign neoplasms. We have examined the presence of mRNA encoding both IGF-I and IGF-II and IGFBP-1, -2, and -3 in fibroids and corresponding myometrium from 20 women undergoing hysterectomy for symptomatic uterine fibroids. Northern blots of total cellular RNA were probed with oligonucleotides for IGF-I, IGF-II, IGFBP-2, and IGFBP-3 and a human IGFBP-1 cDNA. Western ligand blotting was also used to detect the presence of IGFBP proteins in both fibroid and myometrium. The data showed that in fibroids compared to myometrium, 1) the relative abundance of IGF-I mRNA was not different, but there was an increase in the relative abundance of IGF-II mRNA (P < 0.001); 2) IGFBP-1 mRNA was undetectable in fibroids and detectable in only 1 specimen of myometrium; 3) there was no difference in the relative abundance of IGFBP-2 mRNA, but there was an increase in the relative abundance of IGFBP-3 mRNA in myometrium (P < 0.05). By Western ligand blotting, both IGFBP-2 and -3 proteins were present. Our data show that the mRNAs encoding IGF-I, IGF-II, IGFBP-2, and IGFBP-3 are expressed in both fibroids and myometrium and that fibroids express more IGF- II and less IGFBP-3 mRNA than myometrium. We postulate that the net effect of the changes seen is to increase the bioavailability of free (bioactive) IGF, which may then play a major role in promoting fibroid tumor growth.

Objective: To determine the maternal serum concentrations of inhibin, E2, P, and hCG in early pregnancies arising from IVF and ET or GIFT and to assess the value of these hormone measurements in determining outcome of pregnancy. Design(s): Serum immunoactive inhibin, E2, P, and hCG levels were measured in the first trimester of pregnancies after IVF-ET and GIFT procedures. Setting(s): In vitro fertilization and ET or GIFT was undertaken at Monash IVF, Melbourne, Victoria, Australia. Patient(s): At least two blood samples were collected from 117 women between 4 and 11 weeks of gestation. Main Outcome Measure(s): The hormone concentrations in the IVF-ET and GIFT pregnancies were compared with those in pregnancies and related to outcome of pregnancy. Result(s): Serum inhibin levels in singleton pregnancies were significantly higher than in comparable normal pregnancies. In contrast to normal conceptions in which inhibin concentrations rose to peak at 11 weeks, the levels found in IVF-ET and GIFT singleton pregnancies were high at 5 weeks' gestation and declined subsequently. In twin pregnancies, the inhibin levels were significantly greater than those in singleton pregnancies. In biochemical pregnancies diagnosed by increasing hCG concentrations in the absence of an embryonic sac, inhibin levels were significantly lower than those found in singleton pregnancy, as were E2, P, and hCG levels. In anembryonic pregnancies, diagnosed by the confirmation of an intrauterine gestation sac with no evidence of a fetal complex, inhibin concentrations were highest at week 4 and declined, being significantly lower at all stages of gestation. In ectopic pregnancy, serum inhibin levels were lower at all stages of gestation, whereas E2 concentrations were not lower until 6 weeks and P levels until week 5. Serum hCG levels were significantly lower at all stages of gestation. In women with spontaneous abortions, inhibin levels were lower than singleton pregnancies at 7 weeks. Conclusion(

Objective: To examine the relationship of baseline and preovulatory serum E2, P, and LH levels and age with pregnancy outcome in polycystic ovarian syndrome (PCOS) patients undergoing hMG ovulation induction. Design(s): Retrospective analysis of all available data over 2 years. Setting(s): Tertiary referral ovulation induction clinic. Subjects: Forty-four anovulatory PCOS patients with 25 ovulatory nonconception and 50 conception cycles after hMG ovulation induction. Main Outcome Measure(s): Ovulation (midluteal serum P > 25 nmol/L [7.86 ng/mL]); pregnancy (serum beta-hCG > 30 mIU/mL 16 days after ovulating injection); pregnancy outcome: pregnancy termination < 20 weeks' or >=20 weeks' amenorrhea. Result(s): Of the endocrine parameters considered, none was significantly different in nonconceptive and conceptive ovulatory cycles. Miscarriage was associated with low basal serum E2: median value for pregnancies ending <20 weeks, 105 pmol/L (28.6 pg/mL) for >=20 weeks 150 pmol/L (40.9 pg/mL). It was also significantly associated with age. For patients > 29.5 years of age, (29.5 years, population mean age) a baseline E2 <= 140 pmol/L (38.2 pg/mL) had sensitivity 92%, specificity 54%, positive predictive value 65%, and negative predictive value 87% for the prediction of miscarriage. The nature of the previous cycle, the day of the cycle on which therapy commenced, and a past history of miscarriage were not related either to pregnancy outcome or to basal serum E2.

Objective. To compare postoperative pain and recovery of patients undergoing surgery with the 2-mm microlaparosope and the 10-mm standard laparoscope. Design. A double-blind prospective randomized clinical study to assess pain. Setting. Monash Medical Centre Women's Health Program, Melbourne, Australia. Subjects. 29 women of reproductive age (24-45 years) undergoing diagnostic procedures for fertility were randomly allocated to either microlaparoscopy (ML) or standard laparoscopy (SL). Interventions. Of these patients 13 received a microlaparoscopy and 16 received standard laparoscopy. All patients agreed to complete the self- administered Short-Form McGill Pain Questionnaire (SF-MPQ), immediately after surgery before any analgesia and at 48 h after surgery, in order to assess pain and recovery. Main outcome measures. Pain intensity and recovery time for patients undergoing microlaparoscopy were compared with those for standard laparoscopy. Results. There was no significant difference between the two groups when the effective, sensory and visual analogue scale (VAS) pain scores, immediately after recovery and at 48 h, were compared. However there was a significant difference in the time to return to normal activity as perceived by the patients, with the ML group scoring a quicker return to normal activity (mean +/- SD, 3.6 +/- 3.6 compared with the SL group (7.1 +/- 3.3) (P = 0.01). This was despite a significant difference in operating times between the two groups. The mean operating time for the ML group was 22.6 min (95% confidence interval (CI) 18.8-26.5), compared with a mean for the SL group of 16.4 min (95% CI, 13.9-18.8) (P = 0.01). The ML group required no narcotic postoperative analgesia. Conclusion. There was no significant difference in pain scores between groups in whom the microlaparoscope or the standard laparoscope were used. However the microlaparoscopy group experienced a quicker post-surgical recovery, required less analgesia and were more satisfi

Ovarian inhibin production is stimulated by the administration of human menopausal gonadotrophins or following a rise in endogenous LH and FSH. In order to determine whether FSH specifically stimulates inhibin secretion in vivo, immunoassayable serum inhibin levels were measured following the administration of a highly purified preparation of urinary FSH free of significant contamination with LH. Ten anovulatory women underwent a protocol of induction of ovulation with purified FSH and human chorionic gonadotrophin (hCG). During the induction of ovulation, blood samples were taken for radioimmunoassay of FSH, LH, oestradiol, progesterone and inhibin. During the administration of FSH there were increases in plasma concentrations of FSH, oestradiol and inhibin (P < 0.01) but no significant change in the concentration of LH. Oestradiol and inhibin concentrations rose in parallel and were closely correlated (tau = 0.920, n = 110, P < 0.001). There was also a direct correlation between the measured level of FSH and inhibin (tau = 0.512, n = 110, P < 0.05), but there was no correlation between LH and oestradiol, inhibin or FSH. Inhibin (tau- = 0.702, n = 10, P < 0.01) and oestradiol (tau- = 0.691, n = 10, P < 0.01) were correlated with the number of follicles seen on ovarian ultrasound. Levels of oestradiol and inhibin reached a peak on the day of hCG administration or on the following day. Inhibin levels then fell over the next 2 days in all cycles. In an ovulatory cycle resulting in conception, inhibin and oestradiol then rose in parallel with progesterone. We conclude that inhibin appears to be a follicular product which in the follicular phase of the cycle, is stimulated by FSH alone, with granulosa cells being the probable site of production.

Elevated serum immunoreactive inhibin concentrations have been reported in patients with mucinous and granulosa cell tumors of the ovary. The present study aimed to determine whether the inhibins and/or the related peptides, the activins, were demonstrable within ovarian tumor tissue. Immunohistochemical analyses were performed on 11 ovarian tumors, 5 mucinous, 3 serous, 1 granulosa, 1 clear cell, and 1 metastatic colonic cancer. Both monoclonal and polyclonal antisera specific for inhibin-A, activin-A, and activin-B, and their alpha-, beta(B)-, and beta(B)-subunits were used. The mucinous cells of all five mucinous tumors showed positive staining for activin-A and activin-B, and their beta(A)- and beta(B)-subunits, and three stained positive for inhibin-A and the alpha-subunit. The granulosa cell tumor also showed positive staining for inhibin-A and the activins. The remaining tumors were negative. The findings are consistent with the hypersecretion of inhibin (and possibly activin) by some ovarian malignancies and suggest that immunohistochemistry for the inhibins and the activins should be explored further in the classification of ovarian malignancies.

We present these 3 cases to alert others to the possibility of severe pain with rapid shrinkage of fibroids occurring during LHRH analogue treatment. We suggest management of such events should not be surgical except for vaginal excision of prolapsed fibroid polyps.

Objective: To introduce the concept of simulator training to gynaecological surgeons and to inform them of the current state of worldwide research into the development of a laparoscopic simulator. Attributes: Virtual-reality technology enables the surgeon not only to perform diagnostic procedures, but also to practice entire surgical operations on a mannikin, while observing and interacting with a realistic computer-generated gynaecological environment on-screen. The benefits of such simulator training are twofold: surgeons will be at a higher point on the learning curve before their first operation on a patient, and patients should enjoy better quality of care. Research: Great confidence in the potential of virtual-reality technology in gynaecology, and medicine in general, has generated considerable international interest. As a result, much research and development effort is going into the creation of a gynaecological endoscopy simulator. Although several laparoscopic simulators are near their completion stage, there are no commercially available systems as yet. Medical education: A plan for the successful implementation of simulator training in gynaecology through preceptorship and credentialling programs, is outlined. Use of simulator training in gynaecology and other medical fields, is expected to become mole popular with further advances in technology.

Objective: To study whether the effect of cotreatment with human biosynthetic GH improves the outcome of poor IVF responders. Design(s): A double-blind placebo-controlled study using a GnRH agonist (GnRH-a) and gonadotropin in a 'boost' flare-up protocol for ovarian stimulation together with either placebo, 4, or 12 IU of human GH followed by oocyte retrieval and IVF-ET. Patient(s): Twenty-two patients with previously demonstrated poor responses in at least two assisted reproductive technology cycles were recruited. Intervention(s): Pretreatment and post-treatment blood samples and daily morning blood samples during ovarian stimulation were collected after an overnight fast. Human GH or placebo and GnRH-a were administered SC; gonadotropin was administered IM. Oocytes were collected by ultrasound- guided transvaginal aspiration of follicles. Embryos were cultured in vitro and transferred transcervically. Main Outcome Measure(s): Serum E2, FSH, GH, insulin-like growth factor-1 (IGF-I), IGF binding protein 1 (IGFBP-1), and IGFBP-3 concentrations. Number of FSH ampules, follicles, oocytes, embryos, and pregnancies. Result(s): No improvement in cycle outcome was demonstrated with daily adjuvant human GH administration with either 4 or 12 IU. Serum IGF-I levels were highest in the 12 IU human GH group and lowest in the placebo group. Serum IGFBP-3 levels increased 2 days after IGF-I levels in the 12 IU human GH group only. Serum IGFBP-1 levels were unchanged in all groups. Conclusion(s): Poor IVF responders do not benefit from cotreatment with human GH during their ovarian stimulation.

The study was designed to examine (1) the effects of the luteinizing hormone releasing hormone (GnRH) agonist, buserelin, on pituitary and ovarian hormone secretion, and (2) the effect that pituitary-ovarian suppression with a GnRH agonist has on subsequent ovulation induction with exogenous gonadotrophins (hMG), in polycystic ovary syndrome (PCOS). Two protocols were studied where buserelin was administered intranasally to all patients in a dose of 200 mug, six times daily. Ten patients received buserelin until oestrogen withdrawal bleed occurred while a further 12 patients received buserelin for 4 weeks, before hMG was co-administered. Nine of the above subjects also underwent conventional ovulation induction with hMG. Blood samples were taken daily for radioimmunoassay of LH (LH-RIA), FSH , sex steroids and inhibin and for immunoradiometric assay of LH (LH-IRMA). Following buserelin administration there was an initial rise in LH-RIA, FSH, oestradiol (E2) and inhibin (P < 0.01). Fourteen days were needed for LH-RIA to return to the normal range, with both protocols resulting in a fall in LH-RIA and FSH (P < 0.01) before hMG was co-administered. Twenty-eight days of buserelin administration were needed to suppress E2 into the castrate range. Inhibin and both E2 and FSH were closely correlated throughout buserelin administration (P < 0.01). There was failure to respond to an intravenous bolus of 100 mug of GnRH from 7 days of buserelin administration onwards, despite the serum LH-RIA still being raised at 7 days. Serum samples assayed for LH by RIA using WHO Matched Reagents and by IRMA were closely correlated (r = 0.96, P < 0.01). There was no difference in the proportion of ovulations (52% vs 66%) or pregnancies (1 vs 1) in the GnRH agonist or control group. Similar amounts of hMG were needed in both groups and there was multiple follicular development (> 3 follicles > 15 mm diameter; 41% vs 38%) following hMG administration. There was a close correlation between

So far as is known, this is the first series to report the effects of embryo transfers on endometrial integrity as assessed by direct hysteroscopic visualization. Subjects (n = 30) were patients of reproductive age undergoing diagnostic hysteroscopy. A mock embryo transfer was performed by a single clinician, immediately followed by saline hysteroscopy using a 2.7 mm hysteroscope. Hegar dilators or uterine sounds were not used. Representative video clips were recorded for independent assessment of endometrial integrity. (The movie sequence may be purchased for viewing on the internet at www.rbmonline.com/Article/1040; it is free to web subscribers.) Outcomes measured were ease of transfer (easy, moderate, difficult, very difficult) and details of the transfer technique. Endometrial damage was independently assessed and graded as follows: none, minor, moderate or severe. Of the easy transfers, 54% showed no endometrial damage. However, there 37% showed moderate to severe damage in the easy transfer group. Of the moderately difficult transfers, there was no clear association between perceived difficulty of transfer and amount of endometrial damage. Clinical perception of ease of transfer does not correlate well with the degree of endometrial disruption (P = 0.41). Use of hysteroscopy offers a unique insight into the effects of embryo transfer on endometrial integrity.

Objectives: (i) To confirm objectively the efficacy of electrocautery endometrial resection in the treatment of menorrhagia; (ii) to assess argon laser endometrial ablation for menorrhagia and to compare it with electrocautery. Design(s): Prospective, randomized trial. Setting(s): tertiary referral centre, university department. Subjects: Twenty-two patients with subjective menorrhagia. Result(s): both treatment modalities produced statistically comparable improvements in MBL at 3 months (63.8% (SE 7.2%) reduction for laser vs. 81.0% (SE 9.5%) for electrocautery (P = 0.17)) and 6 months (68% (SE 6.6%) laser vs. 78.5% (SE 13%) electrocautery (P = 0.48). The amount of time spent in theatre was considerably greater for the laser cases (114 min (SE 8.7) vs. 80 min (SE 9.4) (P < 0.01)). The incidence of postoperative complications and the amount of analgesia required were similar for the two groups. Two of 12 laser and one of 10 electrocautery cases required a second surgical procedure. Two laser and four electrocautery cases became amenorrhoeic. Conclusion(s): Electrocautery and argon laser produce comparable reductions in objectively confirmed MBL. However, electrocautery is faster and cheaper.

Objectives: The purpose of this study was to perform an audit continuing from the first series of 6500 consecutive laparoscopies from one centre. Since that time there have been a further 4448 consecutive laparoscopies at the same centre, making the total number 11 448 laparoscopies. The debate continues to rage concerning entry techniques at laparoscopy. One of the objectives of this study was to look again at the risks involved with the use of Veress needle and closed trocar entry techniques. Design(s): All the major complications from laparoscopies performed between 1 April 1995 and 28 February 1999 were documented. This is again the largest series to date from any one centre. Each laparoscopy was registered on computer. A distinction between operative and diagnostic laparoscopy was not made. Result(s): A major complication was defined as one which required laparotomy. In this second series, there was only one complication. The incidence of major complications was thus 0.2 per 1000. The incidence in our previous series was 1.23 per 1000. The combined incidence from both series is 0.78 major complications per 1000 cases. In neither series was there a vascular injury as a result of using a Veress needle or closed trocar entry technique. Conclusion(s): This ongoing audit, and in particular the combined figures from both our audits, shows that there is currently no evidence to suggest that the Veress needle should be banned in favour of the open Hasson technique.

The possibility that ovulation induction increases the risk of ovarian cancer remains unproven. However, recent studies suggest that both infertility and endometriosis may be independent risk factors. Despite the various case reports and epidemiological studies performed the association between the use of infertility drugs and ovarian cancer remains weak. The fact that the women who were the first to use ovulation agents are now reaching mid-life means that future studies should show whether any association exists. Hence, there is a need now for large prospective trials to be performed to establish whether an association between ovulation induction agents and ovarian cancer truly exists.

Objective: The hypothesis of this study was that oestrogen may play a role in fibroid growth and that a lack of oestrogen may be the reason for gonadotrophin-releasing hormone agonist (GnRHa) induced fibroid shrinkage. Therefore our aims were (1) to investigate oestrogen receptor (ER) and progesterone receptor (PR) binding in fibroids and myometrium from untreated women and in fibroids from GnRHa pretreated women, (2) to evaluate the mRNA expression of ER and PR in these tissues, and (3) to examine whether a correlation existed between receptor binding and mRNA expression for ER and PR. Design(s): Cytosolic ER and PR binding was assessed by the dextran-coated charcoal technique and ER and PR mRNA expression was assessed using Northern blots of total RNA. Patient(s): Fibroid and corresponding myometrial specimens were obtained from 20 women undergoing hysterectomy while fibroid specimens only were obtained from 10 women undergoing myomectomy after at least 3 months pretreatment with GnRHa. Result(s): We found that (1) ER binding was twice and PR binding was three times as great in fibroid as in myometrium and that there was no difference in binding for either receptor between fibroids from untreated and GnRHa pretreated women, (2) ER and PR mRNA abundances were similar in fibroids and myometrium from untreated women and In fibroids from untreated and GnRHa pretreated women, and (3) ER binding and ER mRNA abundance in both groups of fibroids and myometrium were independent of each other, but there was a positive correlation between PR binding and PR mRNA abundance in untreated fibroids and myometrium but not in GnRHa pretreated tumours. Conclusion(s): We conclude that (1) both oestrogen and progesterone may contribute to fibroid growth because of increased receptor binding in fibroids compared with myometrium and (2) in GnRHa treated women, fibroids may shrink because of a lowered circulating oestradiol level rather than because of a change in steroid receptor binding

BACKGROUND: Obstetric haemorrhages have been reported to be increased after assisted reproduction technologies (ART) but the mechanisms involved are unclear. METHOD(S): This retrospective cohort study compared the prevalence of antepartum haemorrhage (APH), placenta praevia (PP), placental abruption (PA) and primary post-partum haemorrhage (PPH) in women with singleton births between 1991 and 2004 in Victoria Australia: 6730 after IVF/ICSI, 24 619 from the general population, 779 after gamete intrafallopian transfer (GIFT) and 2167 non-ART conceptions in infertile patients. Risk factors for haemorrhages in the IVF/ICSI group were examined by logistic regression. RESULT(S): The IVF/ICSI group had more APH: 6.7 versus 3.6 (adjusted OR 2.0; 95 CI 1.8-2.3), PP: 2.6 versus 1.1 (2.3; 1.9-2.9), PA: 0.9 versus 0.4% (2.1; 1.4-3.0) and PPH: 11.1 versus 7.9% (1.3; 1.2-1.4) than the general population. APH, PP and PA were as frequent in the GIFT group as in the IVF/ICSI group, but were less frequent in the non-ART group. Within the IVF/ICSI group, fresh compared with frozen thawed embryo transfers (FET) was associated with more frequent APH (1.5; 1.2-1.8) and PA (2.1; 1.2-3.7) and the odds ratio increased with number of oocytes collected (1.02; 1.00-1.04). Endometriosis patients had more PP (1.7; 1.2-2.4) and PPH (1.3; 1.1-1.6) than those without endometriosis. FET in artificial cycles was associated with increased PPH (1.8; 1.3-2.6) compared with FET in natural cycles. CONCLUSION(S): SObstetric haemorrhages are more frequent with singleton births after IVF, ICSI and GIFT. The exploratory analysis of factors in the IVF/ICSI group, showing associations with fresh embryo transfers in stimulated cycles, endometriosis and hormone treatments, suggests that events around the time of implantation may be responsible and that suboptimal endometrial function is the critical mechanism.

Objective: To determine whether adverse perinatal outcomes are increased in subfertile women. Design(s): Cohort study. Setting(s): Two tertiary assisted reproductive technologies (ART) centers; Victorian births register. Patient(s): Records of women who registered with the clinics (1991-2000), but did not have an infant using ART, were linked to the birth register (1991-2004) to identify singleton non-ART births within 5 years of registration (N = 2171). Controls, matched by maternal age and year of infant's birth, were selected randomly from birth records (N = 4363). Intervention(s): None. Main Outcome Measure(s): Adverse obstetric and perinatal outcomes. Result(s): After adjusting for confounders, compared with controls, subfertile women had increased odds of hypertension or preeclampsia (adjusted odds ratio [OR] 1.29, 1.02-1.61), antepartum hemorrhage (adjusted OR 1.41, 1.05-1.89), perinatal death (adjusted OR 2.19, 1.10-4.36), low birth weight (adjusted OR 1.44, 1.11-1.85), preterm birth <37 weeks (adjusted OR 1.32, 1.05-1.67) or <31 weeks (adjusted OR 2.37, 1.35-4.13), and cesarean delivery (adjusted OR 1.56, 1.37-1.77). There was weak evidence for increased birth defects (adjusted OR 1.30, 0.98-1.72) and gestational diabetes (adjusted OR 1.25, 0.96-1.63). No increased risk was found for prelabor rupture of membranes, small for gestational age, or postpartum hemorrhage. Conclusion(s): Subfertile women with singleton births are at increased risk of several adverse outcomes. These risks should be considered during their antenatal care and when analyzing adverse effects of ART. Copyright © 2010 American Society for Reproductive Medicine, Published by Elsevier Inc.

Objective: There are currently no programs to assess ovarian health in postmenopausal women. The aim of this study was to describe the ovaries in healthy women at least 5 years after menopause by questionnaire, transvaginal ultrasonography, and blood ovarian cancer markers. Design(s): A total of 515 women who were asymptomatic and at the Stages of Reproductive Aging Workshop +2 stage of menopause (>5 y postmenopause) were recruited by advertisement. Clinical history was obtained by questionnaire, and biophysical assessment by a transvaginal ultrasound investigation and biochemical assessment by serum CA-125 and inhibin were performed. Abnormal findings were confirmed and then reviewed. Result(s): Both ovaries were identified by transvaginal ultrasonography in 71% of women. The right ovary was visualized in 86.3% of these volunteers, and the left ovary was visualized in 78%. The presence of small unilocular cysts and echogenic foci facilitated identification of the ovary in some women. Ovarian/paraovarian lesions were present in 12.6% of women. Abnormalities of the endometrium and uterus were also common, prompting surgery in 7.2% of the women. Total serum inhibin concentrations were normal for postmenopausal women, whereas serum CA-125 was elevated in two women. Conclusion(s): We find that the description and detection of postmenopausal ovaries by transvaginal ultrasonography allows the identification of both ovaries in most postmenopausal women. Ultrasonography-detected abnormalities of the ovary and/or the uterus/endometrium are common in women at this stage of life. The potential need for surgical intervention after the detection of such abnormalities needs to be carefully evaluated when considering transvaginal ultrasonography as a screening tool for ovarian cancer. © 2008 by The North American Menopause Society.