Generating receptive endometrium in Asherman's syndrome.

Intrauterine administration of bone marrow stem/progenitor cells to a woman with thin endometrium refractory to estrogen stimulation regenerated her endometrium sufficiently to support a pregnancy. Or was it local endometrial damage induced by concurrent curettage that stimulated endogenous endometrial stem/progenitor cells into action? Or both?

Adverse obstetric and perinatal outcomes in subfertile women conceiving without assisted reproductive technologies.

OBJECTIVE: To determine whether adverse perinatal outcomes are increased in subfertile women. DESIGN: Cohort study. SETTING: 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). INTERVENTIONS: 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.

Ovarian status in healthy postmenopausal women: follow-up 12 months after transvaginal ultrasound.

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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Perinatal outcomes after assisted reproductive technology treatment in Australia and New Zealand: single versus double embryo transfer.

OBJECTIVE: To compare the perinatal outcomes of babies conceived by single embryo transfer (SET) with those conceived by double embryo transfer (DET). DESIGN, SETTING AND PARTICIPANTS: A retrospective population-based study of embryo transfer cycles in Australia and New Zealand between 2002 and 2006, using data from the Australia and New Zealand Assisted Reproduction Database. MAIN OUTCOME MEASURES: Proportion of SET procedures; comparison of SET and DET procedures with respect to multiple births, low birthweight (LBW), preterm birth and fetal death. RESULTS: The proportion of SET procedures has increased from 28.4% in 2002 to 32.0% in 2003, 40.5% in 2004, 48.2% in 2005 and 56.9% in 2006. The multiple birth rate for all babies conceived by SET (4.0%) was 10 times lower than for those conceived by DET (39.1%) (P < 0.01). The average birthweight for all liveborn babies conceived by SET (3290 g) was higher than for those conceived by DET (2934 g) (P < 0.01). The preterm birth rate of all DET-conceived babies (30.3%) was higher than for SET-conceived babies (12.3%) (adjusted odds ratio [AOR], 3.19 [95% CI, 3.01-3.38]). All babies conceived by DET were more likely to be stillborn than those conceived by SET (AOR, 1.49 [95% CI, 1.21-1.82]). Singletons conceived by DET were more likely to be born preterm than singletons conceived by SET (AOR, 1.13 [95% CI, 1.05-1.22]). Liveborn singletons conceived by DET were 15% more likely to have LBW than liveborn singletons conceived by SET (AOR, 1.15 [95% CI, 1.05-1.26]). There was no significant difference in fetal death rate between DET- and SET-conceived singletons. CONCLUSION: The increase in proportion of SET procedures has resulted in a lower rate of multiple births and in better perinatal outcomes in Australian and New Zealand assisted reproduction programs.

Ovarian status in healthy postmenopausal women.

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: 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. RESULTS: 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. CONCLUSIONS: 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.

Activin-A secretion is increased in the eutopic endometrium from women with endometriosis.

BACKGROUND: Activin is a well-characterised growth and differentiation factor and an important inflammatory mediator. Activin is secreted by normal endometrial glands and stroma and is expressed by endometrial leucocytes. It is also known that the eutopic endometrium from women with endometriosis is functionally different to that from women without endometriosis. In this study, we hypothesise that the endometrial secretion of activin is altered in women with endometriosis. AIMS: To determine whether the expression of inhibin/activin subunits and the secretion of activin-A is different in eutopic endometrium from women with and without endometriosis. METHODS: Endometrial biopsies were obtained from premenopausal, regularly menstruating women with and without endometriosis. Staining intensity for the different inhibin/activin subunits was compared in endometrial and endometriotic biopsies. Activin-A secretion was studied using endometrial explants and endometrial glandular and stromal monolayer cell cultures. RESULTS: The alpha- and betaA-subunits of inhibin/activin were more abundant in eutopic glandular cells from patients with minimal to mild endometriosis compared to women without endometriosis. In patients with endometriosis, the betaB-subunit was more abundant in eutopic stromal cells and endometrial leucocytes. Comparison of paired endometrial and endometriotic biopsies from the same patient did not reveal significant differences for any of the inhibin/activin subunits or activin receptors. Activin-A secretion by glandular and stromal endometrial cells was sevenfold and threefold higher, respectively, in women with endometriosis compared to women without endometriosis. CONCLUSIONS: The expression of inhibin/activin subunits in eutopic endometrium is altered in women with endometriosis, leading to higher levels of activin-A secretion by both glandular cells and stromal cells.

Reliability and validity of an objective assessment instrument of laparoscopic skill.

A novel objective assessment method in reproductive endoscopic surgery could advance surgical education.

Long-term metabolic, cardiovascular and neoplastic risks with polycystic ovary syndrome.

Metabolic abnormalities and obesity have long been associated with the development of cardiovascular disease in the general population. These same features are also associated with polycystic ovary syndrome (PCOS). An increased prevalence of hypertension, dyslipidaemia, obesity and hyperinsulinaemia, as well as changes in coagulation and blood vessel function, provide an explanation as to why women with PCOS are at an increased risk of developing cardiovascular disease over the long term.

What is the most relevant standard of success in assisted reproduction? The singleton, term gestation, live birth rate per cycle initiated: the BESST endpoint for assisted reproduction.

Assisted reproduction programmes do not report success consistently. Rates vary with the definition used. Success must reflect delivery of healthy babies, and the burden of treatment to couples. We report the singleton, term gestation, live birth rate of a baby per assisted reproductive technology cycle initiated for a large IVF programme. We defined assisted reproductive technology cycles as those initiated with the intention of oocyte collection. We examined cycles conducted through Monash IVF in 2001. All women with positive pregnancy tests had first trimester ultrasonography. Obstetric outcomes were recorded. All babies had neonatal examinations conducted by paediatricians. A total of 644 positive pregnancy tests were recorded in 2600 cycles; 509 showed fetal heart motion. Of 448 deliveries, 328 were singleton and 120 were multiple. There were 290 singleton deliveries at term gestation. In 2001, a couple had an 11.1% chance of delivering a singleton, term gestation, live baby per assisted reproductive technology cycle begun. We suggest that delivery of a single, term gestation, live baby per cycle initiated is the most relevant standard of success. This statistic was 11.1% at Monash IVF. We encourage programmes to report this BESST (Birth Emphasizing a Successful Singleton at Term) outcome.

Ignorance of electrosurgery among obstetricians and gynaecologists.

OBJECTIVE: The purpose of this study was to assess the level of skill of laparoscopic surgeons in electrosurgery. DESIGN: Subjects were asked to complete a practical diathermy station and a written test of electrosurgical knowledge. SETTING: 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. METHODS: 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 MEASURES: No improvement in electrosurgery skill in one year of obstetric and gynaecological practice. RESULTS: 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: The study found ignorance of electrosurgery/diathermy among gynaecological surgeons. One year later, skills were no better.

Embryo transfer: hysteroscopic assessment of transfer catheter effects on the endometrium.

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.

Genomics in obstetrics and gynaecology.

With the Human Genome Project complete, and microarray technology progressing rapidly, the study of whole genomes has become a reality. The emerging field of genomics is full of promise, has become a cornerstone of commercial drug development, and looks certain to make a major contribution to clinical practice in the future. There is an increasing number of genomic studies concerned with obstetric and gynaecological conditions. Despite this, clinicians in their busy practices often lack a basic understanding of genomics and the tools involved in generating genome-based information. In the present review, we aim to provide the clinician with a basic overview of genomics--what it is, what tools it uses, and how it may benefit our patients. The existing published reports on genomic studies in the reproductive field is reviewed.

Human cloning 2001.

This review summaries human cloning from a clinical perspective. Natural human clones, that is, monozygotic twins, are increasing in the general community. Iatrogenic human clones have been produced for decades in infertile couples given fertility treatment such as ovulation induction. A clear distinction must be made between therapeutic cloning using embryonic stem cells and reproductive cloning attempts. Unlike the early clinical years of in vitro fertilization, with cloning there is no animal model that is safe and dependable. Until there is such a model, 'Dolly'-style human cloning is medically unacceptable.