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The major indications for the clinical use of oestrogen and progestogen are oral contraception (OC) in young women, and hormonal replacement therapy (HRT) in menopause. Over the past few years, epidemiological data have associated the use of these hormones to different cardiovascular conditions such as myocardial infarction, cerebrovascular disease and venous thromboembolism. This review summarizes the data discussed and the conclusions achieved by the ESHRE Capri Workshop Group, recently published in Human Reproduction. [ABSTRACT FROM PUBLISHER]

To assess the reliability of transvaginal ultrasonography and uterine needle biopsy, used singly or in combination, in the diagnosis of diffuse adenomyosis, a prospective study with pathological confirmation of the diagnosis was performed. A total of 102 premenopausal women scheduled for hysterectomy because of menorrhagia and/or pelvic pain underwent preoperative transvaginal ultrasonography. After removal of the uterus, a single full-thickness myometrial biopsy specimen was taken from along the median line in the upper third of the posterior uterine wall, using a 14-gauge Trucut needle. Adenomyosis was diagnosed by the sonographer by the presence of indistinctly demarcated heterogeneous myometrial areas with distorted echotexture, and by the pathologist when the distance between the lower border of the endometrium and the affected myometrial area was more than one-half of a low power field. The prevalence of adenomyosis was 28% (29/102 patients). The sensitivity and specificity of transvaginal ultrasonography were 82.7 and 67.1% respectively, compared with 44.8 and 95.9% for uterine needle biopsy. The positive predictive values of the two tests were 50.0 and 81.2% respectively, and the negative predictive values 90.7 and 81.4%, likelihood ratios of a positive test 2.5 and 10.9, likelihood ratios of a negative test 0.3 and 0.6, and k indexes of agreement 0.42 and 0.47. Combining the tests did not improve the overall diagnostic performance. Both transvaginal ultrasonography and uterine needle biopsy demonstrated suboptimal test characteristics. [ABSTRACT FROM PUBLISHER]

The evidence of the efficacy of preoperative medical treatment with danazol, gonadotrophin releasing-hormone agonists (GnRHa) or progestins in facilitating surgery and improving the long-term results of myomectomy, hysteroscopic metroplasty and endometrial resection has been reviewed. Sixteen randomized and non-randomized controlled clinical trials, published in the English literature between 1990 and 1996, were identified. In all studies comparing GnRHa or danazol versus no treatment, fluid absorption during surgery was less in subjects who underwent medical treatment independently of the drug used and the type of intervention, the reduction ranging from 142 to 572 ml. A reduction in operating time (between 2 and 25 min) was observed in both the danazol and GnRHa-treated groups in comparison with untreated controls, regardless of the type of operation (endometrial resection, myomectomy or metroplasty). With regard to long-term results, amenorrhoea tended to be more frequent in patients who received GnRHa: the pooled odds ratio (OR) of amenorrhoea for GnRHa-treated women compared with untreated controls was 2.0 [95% confidence interval (CI), 1.1-3.81. In studies comparing GnRHa with danazol, no marked differences were observed in mean operating time, but the OR of amenorrhoea at 6-12 months after surgery was 1.9 (95% CI 1.0-3.3). [ABSTRACT FROM PUBLISHER]

Premature ovarian failure is defined as cessation of ovarian function under the age of 40 years and affects approximately 1% of women in the general population. The aetiology of this disorder is still unknown in most cases. Although there have been some reports of familial premature ovarian failure, very little is known about the incidence and inheritance pattern of its idiopathic form. The aims of this study were to investigate the incidence and inheritance pattern of familial premature ovarian failure in a homogeneous group of patients with premature idiopathic menopause and to identify possible clinical differences between patients with the familial and the sporadic form of premature ovarian failure. A total of 71 women were recruited into the study. Clinical assessments and genetic counselling showed that 22 (31%) patients had familial premature ovarian failure, this high incidence strongly suggesting that the disorder is a recognizable heritable entity. There was a statistically significant (P < 0.05) difference in the median age of precocious menopause in patients with sporadic and familial premature ovarian failure (31.0 and 37.5 years of age in the two groups, respectively). Pedigree analysis strongly suggests the existence of a familial pattern of premature ovarian failure with a dominant maternal and/or paternal transmission and incomplete penetrance. In the presence of familial history of premature ovarian failure, reproductive counselling is recommended. [ABSTRACT FROM AUTHOR]

In order to compare the standard swim-up semen preparation with and without test yolk buffer (TYB) incubation in intrauterine insemination (IUI), we conducted a prospective multicentre randomized trial. A total of 121 infertile couples with male factor (n = 52) or unexplained infertility (n = 69) was randomly assigned to two groups following ovulation induction. Semen was prepared by standard swim-up in group A (n = 64) and by swim-up followed by TYB incubation in group B (n = 57). A maximum of two IUI cycles was performed. A total of 104 cycles was performed in the swim-up group and 90 in the TYB group. Overall, 15 pregnancies were achieved in group A and 23 in group B, with an overall pregnancy rate of 24.8 and 50.0% per patient respectively (χ21, P < 0.05). In the male factor group, pregnancy was achieved in six out of 24 couples (25%) following standard swim-up and in six out of 28 (21.4%) following swim-up and TYB incubation (χ21, not significant). In the unexplained infertility group, pregnancy was recorded in nine out of 40 couples (22.5%) following standard swim-up and in 17 out of 29 couples (58.6%) following swim-up and TYB incubation (χ21, P < 0.05). [ABSTRACT FROM PUBLISHER]

To obtain estimates of the effect of abdominal myomectomy on infertility, information from studies published in the English language literature between 1982 and 1996 was retrieved. Articles were identified through hand and computerized searches using Medline. A total of 27 trials, all published in peer-reviewed journals, was identified, of which four were excluded from the analysis because of methodological limitations. All studies were non-comparative and only nine were prospective. The sample size was generally limited, the mean number of patients included being 49 and the mean number of infertile subjects 26. All patients were followed for at least 12 months after surgery in 12 studies. The combined estimate of pregnancy rates across prospective studies based on a total of 138 observed subjects was 57% [95% confidence interval (CI), 48-65%]. Time to conception varied from a mean of 8 to 20 months. Survival analysis was used in only three studies, with cumulative rates ranging from 57 to 67% at 1 year, and 63% at 5 years. The overall conception rate among seven prospective studies in which only women with otherwise unexplained infertility were recruited was 61% (95% CI, 51-70%) compared with 38% (95% CI, 20-59%) in two prospective studies that included patients with causes of infertility in addition to myomas (χ21 = 4.25, P = 0.04; mean difference = 23%, 95% CI, 1-43%; OR = 2.47, 95% CI, 1.03-5.94). The conception rate ranged from 58 to 65% in the three studies of women with only intramural and/or subserous fibroids and were respectively 53 and 70% in the two that considered only patients with submucous myomas. Data on recurrence after myomectomy were reported in 13 articles, with rates varying from 4 to 47%. According to the available evidence, slightly less than two-thirds of women with uterine leiomyomas and otherwise unexplained infertility conceived after myomectomy. However comparison with expectant management is needed before drawing definitive conclusions on the effectiveness of this time-honoured conservative surgical procedure. [ABSTRACT FROM PUBLISHER]

The obesity 'epidemic' continues to increase, mostly but not only in developed countries. As overweight and obese women are at an increased risk for venous thromboembolism (VTE) at baseline and at a much higher risk during pregnancy, it is essential to help these women to plan pregnancies carefully and to use contraceptives with a positive ratio of benefits versus risks. The Expert Group on hormonal and molecular contraception of the European Society of Contraception convened to review the existing evidence and propose recommendations to the prescribers in line with most recent studies and with the Medical Eligibility Criteria of the World Health Organisation.

BACKGROUND This paper explores recent developments in female contraception, using them to illustrate how adaptation of existing methods, improved service delivery and understanding contraceptive behaviour might increase contraceptive uptake and correct and consistent use, and how the development of new methods holds some promise for capitalizing on the potential non-contraceptive benefits. METHODS Searches were performed in Medline and other databases. Selection criteria included high-quality studies and studies relevant to clinical reproductive medicine. Summaries were presented and discussed by the European Society of Human Reproduction and Embryology (ESHRE) Workshop Group. RESULTS The topics discussed include: adapted regimens for combined oral contraceptive pills, non-invasive methods of female sterilization, the need to improve the awareness of pregnancy risk to increase the use of emergency contraception, improvements in the evidence base for the safety and service delivery of intrauterine methods, emphasis on the potential benefits of combined oral contraceptives for women with hirsutism and acne, the potential of female sterilization to prevent ovarian cancer, and the promise of anti-progesterones and new approaches to dual protection. CONCLUSIONS Although great strides have been made in recent years in increasing contraceptive use among women in many countries where contraceptive prevalence is low or there is a high unmet need for contraception, much more can, and needs to, be done.

Objective: To investigate compliance, satisfaction, and preference in women using a transdermal contraceptive patch., Methods: Women (18-46 years) from eight European countries used contraceptive patches (norelgestromin 6 mg, ethinylestradiol 600 μg) for six, 4-week treatment cycles. Compliance, satisfaction, and preference were assessed after 3 and 6 cycles and study completion using self-report methods., Results: Of the 778 participants, 36.8% (n = 287) used no contraception at baseline. The most common methods were oral contraceptives (67.9%, n = 334) and barrier methods (21.5%, n = 106). Of oral contraception users, 63.5% (n = 212) were satisfied or very satisfied with their previous method, but compliance was poor with 77.8% (n = 260) reporting missed doses. After 3 and 6 cycles, >80% of all included women were satisfied or very satisfied with the patch. At study completion, most participants (73.7%) reported a preference for the patch compared to their previous method. Of 4107 cycles, 3718 (90.5%) were completed with perfect compliance. Two pregnancies occurred during this study, representing a Pearl Index of 0.63. No new safety issues were identified and the patch was well tolerated., Conclusion: Women were highly satisfied with transdermal contraception and preferred this form of family planning over their previous method. Transdermal contraception represents a valuable addition to contraceptive options with potential to offer high compliance and efficacy.

Laparoscopy is the gold standard for the diagnosis of endometriosis. Although some forms of the disease, such as ovarian endometriomas or deep infiltrating lesions, can now be reliably diagnosed using non-invasive instruments, adhesions and superficial implants cannot be identified without surgery. Identification of these latter forms of the disease has been the main rationale for claiming the necessity to identify non-invasive diagnostic tests to detect endometriosis. In this opinion paper, we analyse the pros and cons of the availability of this kind of test in the current context of our knowledge of the disease. In particular, we emphasize that this instrument may be of benefit provided that the test is not used as a screening test.

Background: Rectovaginal endometriosis usually causes distressing pain. Surgical treatment may be effective but is associated with a high risk of morbidity and major complications. Information on the effect of medical alternatives for pain relief in this condition is scarce., Methods: A comprehensive literature search was conducted to identify all the English language published observational and randomized studies evaluating the efficacy of medical treatments on pain associated with rectovaginal endometriosis. A combination of keywords was used to identify relevant citations in PubMed, MEDLINE and EMBASE., Results: A total of 217 cases of medically treated rectovaginal endometriosis were found; 68 in five observational, non-comparative studies, 59 in one patient preference cohort study, and 90 in a randomized controlled trial. An aromatase inhibitor was used in two of the non-comparative studies, vaginal danazol in one, a GnRH agonist in one, and an intrauterine progestin in one. Two estrogen-progestin combinations used transvaginally or transdermally were evaluated in the patient preference study, whereas an oral progestin and an estrogen-progestin combination were compared in the randomized controlled trial. With the exception of an aromatase inhibitor used alone, the antalgic effect of the considered medical therapies was high for the entire treatment period (from 6 to 12 months), with 60-90% of patients reporting considerable reduction or complete relief from pain symptoms., Conclusions: Despite problems in interpretation of data, the effect of medical treatment in terms of pain relief in women with rectovaginal endometriosis appear substantial.

Objective: To assess the use and effectiveness of IVF in a cohort of women undergoing surgery for endometriosis., Design: Cohort study., Setting: University hospital., Patient(s): Four hundred thirty-eight patients who attempted to become pregnant after conservative surgery for endometriosis., Intervention(s): Interview., Main Outcome Measure(s): Pregnancy and IVF use., Result(s): One hundred ninety-four women conceived in vivo (44%). One hundred twenty-four women did not undergo IVF despite their infertility status (51% of the group of women who failed to conceive in vivo). One hundred thirty-nine women underwent at least one IVF attempt. The cumulative rate of IVF use at 36 months of infertility was 33%. The live-birth/ongoing pregnancy rate per started cycle and per patient was 10% and 20%, respectively., Conclusion(s): In a large tertiary care and referral center, IVF played only a minor role in the treatment of endometriosis-associated infertility.

Background: Surgery is often considered the best treatment option in women with symptomatic endometriosis. However, extent and duration of the therapeutic benefit are still poorly defined., Methods: The best available evidence on surgery for endometriosis-associated pain has been reviewed to estimate the effect size of interventions in the most frequently encountered clinical conditions., Results: Methodological drawbacks limit considerably the validity of observational, non-comparative studies on the effect of laparoscopy for stage I-IV disease. As indicated by the results of three RCTs, the absolute benefit increase of destruction of lesions compared with diagnostic only operation in terms of proportion of women reporting pain relief was between 30% and 40% after short follow-up periods. The effect size tended to decrease with time and the re-operation rate, based on long-term follow-up studies, was as high as 50%. In most case series on excisional surgery for rectovaginal endometriosis, substantial short-term pain relief was experienced by approximately 70-80% of the subjects who continued the study. However, at 1 year follow-up, approximately 50% of the women needed analgesics or hormonal treatments. Major complications were observed in 3-10% of the patients. Medium-term recurrence of lesions was observed in approximately 20% of the cases, and around 25% of the women underwent repetitive surgery., Conclusions: Pain recurrence and re-operation rates after conservative surgery for symptomatic endometriosis are high and probably underestimated. Clinicians and patients should be aware that the expected benefit is operator-dependent.

Laparoscopic treatment for endometriosis-associated infertility is gaining widespread popularity supported mostly by uncontrolled studies, but the purported benefit of surgery may be overvalued. We have therefore analysed the best available evidence with the aim of defining an approximate estimate of the effect size of conservative surgery for infertile women with endometriosis in various clinical conditions. The overall increase in post-operative likelihood of conception over background pregnancy rate may be estimated to be between 10 and 25%. The effect of surgery for peritoneal lesions is limited, and an estimate of benefit should be decreased by the fact that preoperative identification of the subjects actually with the condition is unfeasible. The benefit of excision of ovarian endometriomas is difficult to define due to multiple confounding factors and methodological drawbacks in the considered studies. Excision of rectovaginal endometriosis is of doubtful value and associated with worrying morbidity. The role of surgery before, after or as an alternative to IVF needs clarification. In conclusion, the absolute benefit increase of surgery for endometriosis-associated infertility appears smaller than previously believed. Complete and detailed information on risks and benefits of treatment alternatives must be offered to infertile patients to allow unbiased choices between possible options.

Endometriosis is a chronic inflammatory condition that is responsive to management with steroids. The establishment of a steady hormonal environment and inhibition of ovulation can temporarily suppress ectopic implants and reduce inflammation as well as associated pain symptoms. In terms of pharmacological management, the currently available agents are not curative, and treatment often needs to be continued for years or until pregnancy is desired. Similar efficacy has been observed from the various therapies that have been investigated for endometriosis. Accordingly, combined oral contraceptives and progestins, based on their favourable safety profile, tolerability and cost, should be considered as first-line options, as an alternative to surgery and for post-operative adjuvant use. In situations where progestins and oral contraceptives prove ineffective, are poorly tolerated or are contraindicated, gonadotrophin-releasing hormone analogues, danazol or gestrinone may be used. Future therapeutic options for managing endometriosis must compare favourably against existing agents before they can be considered for inclusion into current practice. Finally, as reproductive prognosis is not ameliorated by medical treatment, it is not indicated for women seeking conception.

Objective: The purpose of this study was to compare the postoperative risk of endometrioma recurrence in women using oral contraception and in those undergoing simple observation., Study Design: After laparoscopic excision of ovarian endometriotiomas, a cyclic, low-dose, monophasic oral contraceptive pill (OCP) was offered to women not seeking pregnancy. One month after surgery, and every 6 months afterward, the patients underwent clinical and ultrasonographic assessment., Results: Of the 277 patients who entered the study, 102 used OCP for the entire follow-up period (always users), 129 used OCP discontinuously (ever users), and 46 declined treatment (never users). The median follow-up was 28 months. Recurrent endometriotic cysts were detected in 74 subjects (27%). The 36-month cumulative proportion of subjects free from endometrioma recurrence was 94% in the always users compared with 51% in the never users (P < .001); adjusted incidence rate ratio (IRR) = 0.10 (95% CI, 0.04-0.24)., Conclusion: Regular postoperative use of OCP effectively prevents endometrioma recurrence.

Abnormal bleeding is a significant health problem, especially during adolescence and before menopause when anovulatory cycles are common. Curettage is rarely necessary to investigate or treat menstrual problems in adolescents, and its use should also be minimized in women younger than 40 years. In every age group, medical treatment is the initial choice, but surgical treatment by endometrial destruction or hysterectomy is sometimes required. Benign causes of bleeding include fibroids and possibly adenomyosis, but the indications for treatment in each case depend upon the extent of bleeding, not the extent of the lesion. Breakthrough bleeding (BTB) with combined oral contraceptives commonly leads to discontinuation of the method. As BTB tends to improve with time, in the first 3 months of pill use, unless there are obvious underlying causes, women should be reassured that it will likely settle. BTB is often the reason for discontinuing progestogen-only contraception, and there is a need for effective means of treating unscheduled bleeding. Bleeding occurs in approximately 3% of post-menopausal women, and the use of hormones increases the likelihood of bleeding by >5-fold. Knowledge of the underlying mechanisms of bleeding is essential to the development of effective treatment.

Observational epidemiological studies aimed at elucidating the relationship between fibroids and infertility are inconclusive due to methodological limitations. However, two main pieces of clinical evidence support the opinion that the fibroids interfere with fertility. First, in IVF cycles, the delivery rate is reduced in patients with fibroids but is not affected in patients who have undergone myomectomy. Second, even if randomized studies are lacking, surgical treatment appears to increase the pregnancy rate: approximately 50% women who undergo myomectomy for infertility, subsequently conceive. Available evidence also suggests that submucosal, intramural and subserosal fibroids interfere with fertility in decreasing order of importance. Although more limited, some data supports an impact of the number and dimension of the lesions. Drawing clear guidelines for the management of fibroids in infertile women is difficult due to the lack of large randomized trials aimed at elucidating which patients may benefit from surgery. At present, physicians should pursue a comprehensive and personalized approach clearly exposing the pros and cons of myomectomy to the patient, including the risks associated with fibroids during pregnancy on one hand, and those associated with surgery on the other hand.

Background: If the menstrual reflux or implantation theory of endometriosis is true, refluxed endometrial cells could reach the right hypochondrium transported by the clockwise peritoneal fluid current and would implant more easily on the right diaphragmatic leaf as they are stuck there by the falciform ligament., Methods: To investigate if a lateral asymmetry exists in diaphragmatic endometriotic lesion distribution, all articles on diaphragmatic endometriosis identified by MEDLINE, EMBASE and PUBMED database searches were retrieved, and additional reports were collected by systematically reviewing all references. The number of women and the side of the lesion with respect to the falciform ligament of the liver were obtained from individual studies, and the combined frequency of right- and left-side diaphragmatic endometriosis was computed. In addition, seven personal cases were described., Results: There were 16 reports including 47 subjects selected. Diaphragmatic endometriosis was on the right side in 31 (66%) patients, on the left in 3 (6%) and bilateral in 13 (27%). In the personal series, lesions were on the right side in five cases, on the left in one and bilateral in one. Considering only unilateral lesions, the observed proportion of right-sided endometriotic implants (36/40) was 90% (95% CI 76-97%; chi(2)(1) 32.6, P < 0.0001)., Conclusions: The observed major asymmetry in diaphragmatic endometriotic lesion distribution in favour of the right leaf supports the menstrual reflux theory.

Background: The usefulness of GnRH antagonists in mild controlled ovarian hyperstimulation (COH) and intrauterine insemination (IUI) cycles is debated., Methods: Two-hundred and ninety-nine couples with unexplained or mild male factor infertility were enrolled in this international multicentre randomized controlled trial. Women allocated to the GnRH antagonist group (n=148) received 50 IU recombinant FSH starting on day 3 of the menstrual cycle and Ganirelix 0.25 mg daily starting from the day in which a follicle with a mean diameter of 13-14 mm was visualized at ultrasound. Women allocated to the control group (n=151) were administered only 50 IU recombinant FSH starting on day 3 of the menstrual cycle. Couples were recruited only for their first treatment cycle. The primary outcome was the clinical pregnancy rate per initiated cycle., Results: Baseline characteristics of the two treatment groups were similar. Clinical pregnancy rates per initiated cycle in women who did and did not receive GnRH antagonists were 12.2 and 12.6%, respectively (P=1.00). The relative risk of conception (95% confidence interval) for the use of GnRH antagonists was 1.0 (0.5-1.9)., Conclusions: In mild COH and IUI cycles, any benefit of the use of GnRH antagonists in improving pregnancy rates is <2-fold increase.

Background: The association between lesion type, disease stage and severity of pain was studied in a large group of women with endometriosis to verify whether endometrial implants at different sites determine specific complaints and to evaluate the validity of the current classification system in women with symptomatic disease., Methods: A total of 1054 consecutive women with endometriosis undergoing first-line conservative or definitive surgery were included. Data on age at surgery, disease stage according to the revised American Fertility Society (AFS) classification, anatomical characteristics of endometriotic lesions, and type and severity of pain symptoms were collected and analysed by multiple logistic regression., Results: Minimal endometriosis was present in 319 patients, mild in 139, moderate in 292 and severe in 304. A significant inverse relationship was demonstrated between age at surgery and moderate-to-severe dysmenorrhoea, dyspareunia and non-menstrual pain. A strong association was found between posterior cul-de-sac lesions and pain at intercourse [Wald chi (2) = 17.00, P = 0.0001; odds ratio (OR) = 2.64, 95% confidence interval (CI) = 1.68-4.24]. A correlation between endometriosis stage and severity of symptoms was observed only for dysmenorrhoea (Wald chi (2) = 5.14, P = 0.02) and non-menstrual pain (Wald chi (2) = 5.63, P = 0.018). However, the point estimates of ORs were very close to unity (respectively, 1.33, 95% CI = 1.04-1.71, and 1.01, 95% CI = 1.00-1.03)., Conclusions: The association between endometriosis stage and severity of pelvic symptoms was marginal and inconsistent and could be demonstrated only with a major increase in study power.

Objective: This study was undertaken to ascertain whether the incidence of pregnancy is increased and time-to-conception is reduced in infertile women with rectovaginal endometriosis undergoing conservative surgery compared with those on expectant management., Study Design: A total of 105 infertile women under the age of 40 years with rectovaginal endometriosis and no other associated major infertility factor underwent first-line conservative surgery at laparotomy or expectant management according to a shared decision-making approach., Results: Among the 44 women who had resection of rectovaginal endometriosis, 15 became pregnant, compared with 22 of the 61 women who choose expectant management (24-month cumulative probabilities, 44.9% and 46.8%, respectively; log-rank test, chi2(1) = 0.75; P = .38). One major and 9 minor postoperative complications occurred. Significant differences in pain-free survival time in favor of the surgery group were observed for dysmenorrhea, dyspareunia, and dyschezia., Conclusion: Conservative surgery for rectovaginal endometriosis in infertile women does not modify the reproductive prognosis although it does increase pain-free survival time.