European society of contraception statement on contraception in obese women.

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.

Family planning 2011: better use of existing methods, new strategies and more informed choices for female contraception.

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.

Non-invasive diagnosis of endometriosis: the goal or own goal?

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.

Satisfaction and compliance in hormonal contraception: the result of a multicentre clinical study on women's experience with the ethinylestradiol/norelgestromin contraceptive patch in Italy.

BACKGROUND: For many women finding the right contraceptive method can be challenging and consistent and correct use over a lifetime is difficult. Even remembering to take a birth control pill every day can be a challenge. The primary objective of this study was to evaluate women's experience with a weekly ethinylestradiol/norelgestromin contraceptive patch (EE/NGMN patch), given new technologies recently developed in hormonal contraception to increase women's options in avoiding daily dosing. METHODS: In 24 Italian sites, 207 women received the EE/NGMN patch for up to 6 cycles. At study end, overall satisfaction and preference, as well as compliance, efficacy and safety, were evaluated. RESULTS: 175 women (84.5%) completed the study. The overall satisfaction rate was 88%; convenience and once-a-week frequency of the patch were especially appreciated. At baseline, 82 women (39.4%) were using a contraceptive method, mainly oral contraceptives and barrier methods, but only 45.1% were very satisfied/satisfied; after 6 months with the patch, 86.3% of this subset was very satisfied/satisfied. Considering the method used in the 3 months before the study entry, 78.1% strongly preferred/preferred the patch, for convenience (53.9%), ease of use/simplicity (28.9%), fewer (9.2%) and less severe (2.6%) side effects. Compliance was very high: 1034/1110 cycles (93.2%) were completed with perfect compliance and the mean subject's compliance score was 90%. One on-therapy pregnancy occurred. The patch was safe and well tolerated: adverse events frequency was low, with predominantly single reports of each event. Most of them started and subsided during cycle 1. CONCLUSION: This study demonstrated that the EE/NGMN patch is associated with high satisfaction levels and excellent compliance. At study end, the majority of women indicated that they would continue using the patch.

Medical treatment for rectovaginal endometriosis: what is the evidence?

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.

Endometriosis: current therapies and new pharmacological developments.

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.

Surgery for endometriosis-associated infertility: a pragmatic approach.

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.

The use and effectiveness of in vitro fertilization in women with endometriosis: the surgeon's perspective.

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.

Postoperative oral contraceptive exposure and risk of endometrioma recurrence.

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.

Endometriosis: current and future medical therapies.

Endometriosis is a chronic inflammatory disease that responds to steroidal manipulation. Creation of a steady hormonal environment with inhibition of ovulation temporarily suppresses the ectopic implants and reduces the inflammatory status as well as the associated pain symptoms. Pharmacological management of endometriosis must be set within the framework of long-term therapeutic strategies. As the available drugs are not curative, treatments will need to be administered for years or until women desire a pregnancy. The various therapies studied have shown similar efficacy. Consequently, based on a more favourable profile in terms of safety, tolerability and cost, combined oral contraceptives and progestins should be considered as the first-line option, both as an alternative to surgery and as a postoperative adjuvant measure. Gonadotrophin-releasing hormone analogues, danazol and gestrinone should be used when progestins and oral contraceptives fail, are not tolerated or are contra-indicated. Future therapies for endometriosis must compare favourably with existing drugs before hypothesizing their implementation in current practice. Medical treatment is not indicated in women seeking conception because reproductive prognosis is not ameliorated.

Reproductive performance, pain recurrence and disease relapse after conservative surgical treatment for endometriosis: the predictive value of the current classification system.

BACKGROUND: To assess the predictive value of the current classification of endometriosis in terms of response to surgical treatment, we studied to what extent disease stage, lesion type and lesion site were associated with post-operative pregnancy rate, symptom recurrence and disease relapse. METHODS: A total of 729 women with endometriosis undergoing first-line conservative laparoscopic surgery were included. Data on age at surgery, disease stage according to the revised American Fertility Society (AFS) classification, anatomical characteristics of endometriotic lesions, fertility status and types and severity of pain symptoms were collected. RESULTS: Minimal endometriosis was present in 222 patients, mild in 106, moderate in 197 and severe in 204. The cumulative probability of pregnancy at 3 years from surgery in 537 infertile women was 47% (51% at stage I, 45% at stage II, 46% at stage III and 44% at stage IV; log-rank test, chi(2)3=1.50, P=0.68). The cumulative probability of moderate or severe dysmenorrhoea recurrence in 425 symptomatic subjects was 24% (32% at stage I, 24% at stage II, 21% at stage III and 19% at stage IV; log-rank test, chi2(3)=6.39, P=0.094). The cumulative probability of disease relapse was 12% (3% at stage I, 11% at stage II, 11% at stage III and 23% at stage IV; log-rank test, chi(2)3=24.95, P=0.0001). Using Cox's multivariate proportional hazards regression analysis, no association was observed between endometriosis stage or lesion type and lesion site and any of the considered study outcomes. CONCLUSIONS: The current classification of endometriosis has an inadequate predictive value with regard to the major clinical outcomes.

Reproductive performance in infertile women with rectovaginal endometriosis: is surgery worthwhile?

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.

Does laparoscopic removal of nonendometriotic benign ovarian cysts affect ovarian reserve?

BACKGROUND: The objective of this study was to investigate whether laparoscopic excision of nonendometriotic benign ovarian cysts is associated with a significant injury to ovarian reserve. METHODS: Women selected for IVF-ICSI cycles who previously underwent laparoscopic excision of a monolateral nonendometriotic benign ovarian cyst were retrospectively identified. The operated ovary and the contralateral intact gonad of the same patient were compared in term of basal ovarian volume before initiating ovarian stimulation and number of dominant follicles at the time of human chorionic gonadotropin administration. Non-parametric Wilcoxon Rank test was used to investigate differences between the two ovaries. RESULTS: Seventeen cases were recruited. The numbers of dominant follicles were 4.6 +/- 2.5 and 2.7 +/- 2.4 in the control ovary and in the previously operated ovary, respectively (p = 0.01). This drop corresponded to a mean reduction of 42% (95% confidence interval: 10-74%). Basal volumes of the intact and the operated gonads were 5.7 +/- 3.3 and 3.4 +/- 2.3 cm3 respectively (p = 0.01), corresponding to a mean reduction of 39% (95% confidence interval: 12-66%). CONCLUSIONS: Laparoscopic excision of nonendometrioid benign ovarian cysts is associated with a significant injury to ovarian reserve.

Preventing high-order multiple pregnancies during controlled ovarian hyperstimulation and intrauterine insemination: 3 years' experience using low-dose recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonists.

OBJECTIVE: To employ protocols of mild ovarian stimulation to prevent an excessively elevated rate of high-order multiple pregnancies. DESIGN: Case series. SETTING: University hospital. PATIENT(S): Six hundred and twenty one consecutive patients undergoing 1,259 controlled ovarian hyperstimulation and intrauterine insemination cycles. INTERVENTION(S): Patients received 50 IU per day of recombinant follicle-stimulating hormone (FSH) starting the third day of the cycle, then a gonadotropin-releasing hormone (GnRH) antagonist on the day in which a follicle > or =13 mm was visualized. Cycles were canceled if three or more follicles > or =16 mm and/or five or more follicles > or =11 mm were detected. MAIN OUTCOME MEASURE(S): Rate of high-order multiple pregnancies. RESULT(S): The clinical pregnancy rate per initiated cycle was 9.2% (95% confidence interval, 7.5-11.1%). The incidence of twins and high-order multiple pregnancies was 9.5% (95% CI, 5.3-16.2%) and 0 (0.0-3.2%), respectively. CONCLUSION(S): In controlled ovarian hyperstimulation and intrauterine insemination cycles, a protocol of 50 IU of recombinant FSH daily combined with the use of GnRH antagonists and a policy of strict cancellation based on echographic criteria are associated with a satisfactory pregnancy rate per initiated cycle and a low risk of high-order multiple pregnancies.

Should endometriomas be treated before IVF-ICSI cycles?

The laparoscopic excision of ovarian endometriomas appears to increase the chances of spontaneous conception, but the value of this treatment in women selected for IVF-ICSI cycles is debated. Studies recruiting women with unilateral disease and comparing ovarian responsiveness in the affected and contralateral intact gonads indicate that excision of endometriomas is associated with a quantitative damage to ovarian reserve. There are no randomized trials comparing laparoscopic excision to expectant management before IVF-ICSI cycles. The idea that surgery increases IVF pregnancy rates is not supported by the available evidence. However, the chance of conception is not the only issue that has to be considered. Some potential drawbacks are associated with both therapeutical strategies. Specifically, costs and hazard of surgical complications support expectant management whereas oocyte retrieval risks, the possibility of missing occult malignancy and endometriosis progression due to ovarian stimulation would favour surgical treatment. Alternative therapeutical options include medical treatment and ultrasound-guided aspiration. Whereas prolonged GnRH agonist down-regulation may be beneficial, data on ultrasound aspiration are more controversial.

Current treatment issues in female hyperprolactinaemia.

High prolactin levels can occur as a physiological condition in females who are pregnant or lactating. As a pathological condition, hyperprolactinaemia is associated with gonadal dysfunction, infertility and an increased risk of long-term complications including osteoporosis. The most frequent cause of persistent hyperprolactinaemia is the presence of a micro- (<10mm diameter) or macroprolactinoma (>/=10mm). These pituitary tumours may produce an excessive amount of prolactin or disrupt the normal delivery of dopamine from the hypothalamus to the pituitary; prolactin secretion from the pituitary is inhibited by dopamine released from neurones in the hypothalamus. Medications including anti-psychotics can induce hyperprolactinaemia, while idiopathic hyperprolactinaemia accounts for 30-40% of cases. The prevalence of hyperprolactinaemia is difficult to establish as not all sufferers are symptomatic or concerned by their symptoms and may remain undiagnosed. Symptoms of hyperprolactinaemia include signs of hypogonadism, with oligomenorrhoea, amenorrhoea and galactorrhoea frequently observed. Pharmacological intervention should be considered the first line therapy and involves the use of dopamine agonists to reduce tumour size and prolactin levels. Bromocriptine has the longest history of use and is a well-established, inexpensive, safe and effective therapy option. However, bromocriptine requires multiple daily dosing and some patients are resistant or intolerant to this therapy. The two newer dopamine agonists, quinagolide and cabergoline, provide more effective and better tolerated treatments compared with bromocriptine and may offer effective therapies for bromocriptine-resistant or intolerant patients. Quinagolide can be used until pregnancy is confirmed and may result in improved compliance in females wishing to become pregnant. For patients with hyperprolactinaemia, pregnancy is safe and can frequently be beneficial, inducing a decrease in prolactin levels. There does not appear to be any increased risk of abortion, malformations or multiple births in pregnancies achieved with bromocriptine and this dopamine agonist can be used safely during pregnancy. Surgery should be considered only in certain circumstances, and for the majority of patients, dopamine agonists will be sufficient to alleviate symptoms and restore normal prolactin levels.

Damage to ovarian reserve associated with laparoscopic excision of endometriomas: a quantitative rather than a qualitative injury.

OBJECTIVE: Retrospective studies suggest that laparoscopic excision of endometriomas is associated with a reduced responsiveness to ovarian hyperstimulation. In this study, we prospectively evaluated ovarian response to hyperstimulation in women selected for in vitro fertilization and intracytoplasmic sperm injection cycles who previously underwent laparoscopic enucleation of a monolateral endometrioma. STUDY DESIGN: Operated and contralateral intact ovaries of the same patient were compared in terms of number of follicles, number of oocytes retrieved, fertilization rate, and rate of high-quality embryos. RESULTS: Thirty-eight subjects were included. A reduced number of dominant follicles, oocytes, embryos, and high-quality embryos was observed in the operated gonad. The mean percentage of reduction was 60% (95% confidence interval 38-81%), 53% (95% confidence interval 30-75%), 55% (95% confidence interval 28-81%), and 52% (95% confidence interval 17-87%), respectively. Fertilization rate and rate of good-quality embryos were similar. CONCLUSION: Laparoscopic excision of endometriomas is associated with a quantitative but not a qualitative damage to ovarian reserve.

Treatment of symptomatic rectovaginal endometriosis with an estrogen-progestogen combination versus low-dose norethindrone acetate.

OBJECTIVE: To evaluate the efficacy, safety, and tolerability of an estrogen-progestogen combination versus low-dose norethindrone acetate in the treatment of persistent pain after surgery for symptomatic rectovaginal endometriosis. DESIGN: Randomized controlled trial. SETTING: Academic center. PATIENT(S): Ninety women with recurrent moderate or severe pelvic pain after unsuccessful conservative surgery for symptomatic rectovaginal endometriosis. INTERVENTION(S): Twelve-month, continuous treatment with oral ethinyl E2, 0.01 mg, plus cyproterone acetate, 3 mg/day, or norethindrone acetate, 2.5 mg/day. MAIN OUTCOME MEASURE(S): Degree of satisfaction with therapy. RESULT(S): Seven women in the ethinyl E2 plus cyproterone acetate arm and five in the norethindrone acetate arm withdrew because of side effects (n=5), treatment inefficacy (n=6), or loss to follow-up (n=1). At 12 months, dysmenorrhea, deep dyspareunia, nonmenstrual pelvic pain, and dyschezia scores were substantially reduced without major between-group differences. Both regimens induced minor unfavorable variations in the serum lipid profile. According to an intention-to-treat analysis, 28 (62%) out of 45 patients in the ethinyl E2 plus cyproterone acetate group and 33 (73%) out of 45 in the norethindrone acetate group were satisfied with the treatment received. CONCLUSION(S): Low-dose norethindrone acetate could be considered an effective, tolerable, and inexpensive first-choice medical alternative to repeat surgery for treating symptomatic rectovaginal endometriotic lesions in patients who do not seek conception.

Breast cancer risk with postmenopausal hormonal treatment.

This review was designed to determine from the best evidence whether there is an association between postmenopausal hormonal treatment and breast cancer risk. Also, if there is an association, does it vary according to duration and cessation of use, type of regimen, type of hormonal product or route of administration; whether there is a differential effect on risk of lobular and ductal cancer; and whether hormone treatment is associated with breast cancers that have better prognostic factors? Data sources for the review included Medline, the Cochrane Database of Systematic Reviews (Cochrane Library, 2005) and reference lists in the identified citations. Eligible citations addressed invasive breast cancer risk among postmenopausal women and involved use of the estrogen products with or without progestin that are used as treatment for menopausal symptoms. Abstracted data were demographic groupings, categories of hormone use, categories of breast cancer, two-by-two tables of exposure and outcome and adjusted odds ratios, relative risks (RRs) or hazard rates. Average estimates of risk were weighted by the inverse variance method, or if heterogeneous, using a random effects model. The average risk of invasive breast cancer with estrogen use was 0.79 [95% confidence interval (95% CI) = 0.61-1.02] in four randomized trials involving 12 643 women. The average breast cancer risk with estrogen-progestin use was 1.24 (95% CI = 1.03-1.50) in four randomized trials involving 19 756 women. The average risks reported in recent epidemiological studies were higher: 1.18 (95% CI = 1.01-1.38) with current use of estrogen alone and 1.70 (95% CI = 1.36-2.17) with current use of estrogen-progestin. The association of breast cancer with current use was stronger than the association with ever use, which includes past use. For past use, the increased breast cancer risk diminished soon after discontinuing hormones and normalized within 5 years. Reasonably adequate data do not show that breast cancer risk varies significantly with different types of estrogen or progestin preparations, lower dosages or different routes of administration, although there is a small difference between sequential and continuous progestin regimens. Epidemiological studies indicate that estrogen-progestin use increases risk of lobular more than ductal breast cancer, but the number of studies and cases of lobular cancer remains limited. Among important prognostic factors, the stage and grade in breast cancers associated with hormone use [corrected] do not differ significantly from those in non-users, but breast cancers in estrogen-progestin users are significantly more likely to be estrogen receptor (ER) positive. In conclusion, valid evidence from randomized controlled trials (RCTs) indicates that breast cancer risk is increased with estrogen-progestin use more than with estrogen alone. Epidemiological evidence involving more than 1.5 million women agrees broadly with the trial findings. Although new studies are unlikely to alter the key findings about overall breast cancer risk, research is needed, however, to determine the role of progestin, evaluate the risk of lobular cancer and delineate effects of hormone use on receptor presence, prognosis and mortality in breast cancer.