journalScan ovairan,ovary,ovarian cyst,overian,cysts,cystiic,ovarion,cyctic,cystic <b>Peter Kovacs, MD</b>, Albert Einstein College of Medicine, New York, NY, contributes this issue, which focuses on recent publications relating to gynecology and gynecologic endocrinology, with clinical commentary. Short summaries of feature articles include links to the article abstracts and full text, when available. Medscape Medscape Ob/Gyn &amp; Women's Health 10/22/2001 6 2 <H3>Human Reproduction</H3><FONT SIZE="1">From</font> <FONT SIZE="3"><B><i>Human Reproduction</i></B></font><FONT SIZE="2"><b>September 2001 (Volume 16, Number 9)</b></font><p><h4>Medical Management of Early Fetal Demise Using a Combination of Mifepristone and Misoprostol</h4> <FONT SIZE="2"> Wagaarachchi PT, Ashok PW, Narvekar N, Smith NC, Templeton A<BR><i>Human Reproduction</i>. 2001;16(9):1849-1853<P></font><FONT SIZE="2"><h3>Summary</h3> <EM>The combination of mifepristone and vaginal misoprostol is an effective, safe, and well-tolerated method of treatment for first-trimester missed abortion.</EM><P> This study reports experience with mifepristone and misoprostol in the management of early missed abortion. Between 1998 and 1999, women with the diagnosis of missed abortion between 6 and 13 weeks gestation were offered surgical or medical treatment. This study reports experience based on 220 cases of medical management. Participants were treated with 200 mg oral mifepristone. If miscarriage did not occur, 36-48 hours later they were given 800 mcg vaginal misoprostol. Another 2 doses of 400 mcg misoprostol were given 3 hours apart, if necessary. Those who did not pass products of conception were offered surgical treatment or repeat medical treatment. Successful treatment was defined as completed abortion with mifepristone alone or in combination with misoprostol. Two thirds of the participants were diagnosed with missed abortion, one third with anembryonic gestation (empty sac). Demographic data in these 2 groups were analyzed separately and compared. Baseline demographic characteristics (age, parity, number of previous miscarriages) were similar for the 2 groups.<P> About 65% of patients were symptomatic at presentation in both groups. The mean gestational age was 10.1 weeks. Forty patients miscarried after mifepristone alone. Another 145 patients miscarried after misoprostol. Overall success was 84.1%. Medical management failed in 21% of participants who were symptomatic at presentation compared with 6.4% of asymptomatic patients. Eight patients needed to undergo emergent suction curettage secondary to heavy bleeding. It took an average of 8 hours to complete miscarriage. One third of patients required no analgesia, while two thirds received oral or parenteral analgesics. Overall success rate with medical treatment was 93.5% among asymptomatic patients and 78.8% among symptomatic patients. The combination of mifepristone and vaginal misoprostol is an effective, safe, and well-tolerated method for the treatment of first-trimester missed abortion.<P> <h3>Clinical Commentary</h3> This study evaluated a form of medical management of first-trimester missed abortion. Alternative methods are expectant management or surgical evacuation of the uterine cavity. Mifepristone is a progesterone receptor antagonist that disrupts connection between the uterine lining and the products of conception. Misoprostol is a prostaglandin analogue that initiates uterine contractions and facilitates the passage of products of conception. <P> This study is the largest published series of patients treated with mifepristone and misoprostol. All patients who opted for medical management are included. We do not know what percentage of eligible patients chose surgical treatment and whether they were different from the participants of this study. Twenty percent of participants miscarried with mifepristone alone. It is not clear whether these were the initially symptomatic patients. One would think that medical treatment would be more successful among symptomatic patients (eg, those with bleeding or pain), in whom the miscarriage had already begun spontaneously. Of note is that this study found medical treatment to be more successful among asymptomatic women. It is possible that asymptomatic patients were more compliant with medical treatment. It takes significantly longer to achieve completed miscarriage with medical treatment when compared with surgery. <P> Some patients will not want to experience the miscarriage or be exposed to the bleeding and cramping pain accompanying it. It is important to counsel patients regarding the side effects of medical treatment and to provide them with adequate analgesics. This will improve compliance and success rate. A previous study reported an 83% success rate with lower-dose misoprostol alone in similar patients. In this study with mifepristone and higher-dose misoprostol, the success rates were similar. Therefore, the benefit of adding mifepristone to the regimen is questionable. Future studies should compare regimens with mifepristone and misoprostol to similar-dose misoprostol alone for the management of first-trimester missed abortion. Misoprostol with or without mifepristone is a safe, well tolerated, and effective alternative to surgical treatment in the management of first-trimester missed abortion.</font><p><FONT SIZE="2"><A HREF="http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11527887&dopt=Abstract">Abstract</A><P></font><CENTER><HR WIDTH=50%></CENTER><P><FONT SIZE="1">From</font> <FONT SIZE="3"><B><i>Human Reproduction</i></B></font><FONT SIZE="2"><b>July 2001 (Volume 16, Number 7)</b></font><p><h4>Vaginal Misoprostol as Medical Treatment for First Trimester Spontaneous Miscarriage</h4> <FONT SIZE="2"> Ngai SW, Chan YM, Tang OS, Ho PC<BR><i>Human Reproduction</i>. 2001;16(7):1493-1496<P></font><FONT SIZE="2"><h3>Summary</h3> <EM>The use of low-dose vaginal misoprostol is an effective and safe management option for first-trimester missed abortion. It is superior to expectant management.</EM> <P> This study evaluated the use of vaginal misoprostol, a prostaglandin analogue, in the management of first-trimester spontaneous miscarriage. Sixty women were recruited. They were all &gt; 16 years of age, healthy, and had an intrauterine pregnancy verified by ultrasound. All gestations were &lt; 12 weeks. All pregnancies were missed abortions (empty gestational sac, no fetal cardiac activity, no interval growth). Some patients were diagnosed with incomplete abortion on the basis of open cervical os and disrupted endometrium, as detected by ultrasound. Women with severe blood loss, completed abortion, allergy to prostaglandins, or sepsis were excluded. <P> Participants were randomized to expectant management or to vaginal prostaglandin (400 mcg) every other day. Patients in both arms of the study were assessed for adverse effects, need for surgical uterine evacuation, and completed abortion. If after 15 days the patient did not pass gestational products, suction curettage was performed. Successful treatment was defined as no need for surgical intervention until spontaneous menstruation; failure was defined as need for surgical intervention or change of patient's mind about treatment assignment. Baseline characteristics were similar between the 2 groups, except that history of previous pregnancy termination was higher in the misoprostol group. In the expectant management group, more women were diagnosed with incomplete abortion before randomization (36.7% vs 16.7%). Complete abortion rate was significantly higher in the misoprostol group (83.3% vs 48.3%). Method failure was responsible for failed treatment in 2 cases in the misoprostol group and in 7 cases in the expectant management group. The rest of the failures were attributed to either the patient's or to the treating physician's decision. Three women in the expectant management group and 1 in the misoprostol group needed emergency curettage. Side effects and number of days with vaginal bleeding were similar in the 2 groups. This study showed that the use of low-dose vaginal misoprostol is an effective and safe management option for first-trimester missed abortion. It is superior to expectant management.<P> <h3>Clinical Commentary</h3> There are several treatment options that one can offer to patients with first-trimester missed abortions. Surgical treatment is very effective but carries the risk of surgical complications or complications with anesthesia. The use of mifepristone (a progesterone antagonist) in combination with misoprostol is an effective medical method to evacuate the uterus in the early first trimester. Expectant management is another option. This study evaluated the use of misoprostol alone for the treatment of first-trimester missed abortion. The use of misoprostol was compared with expectant management. Sample size was calculated on the basis of a 60% presumed success rate with misoprostol and a 20% success rate with expectant management. <P> Patients in the 2 groups were similar except that there were more patients with incomplete abortion in the expectant group. One would expect a higher success rate in these cases. The gestational ages, as determined by ultrasound, were not known in the 2 groups. Differences in gestational ages can influence the outcome, as medical treatment is more effective in earlier gestations. One would expect fewer complications (eg, significant bleeding) with early pregnancies. <P> Complications of expectant and medical management could be prolonged, with the possibility of heavy bleeding necessitating surgical intervention, nausea, vomiting, abdominal pain, and infection. Emergent suction curettage was rare in this study, and other adverse effects were similar with the 2 treatments. A relatively low dose of misoprostol was used to reduce the incidence of side effects. Increasing the dose could lead to improved success and faster response, although at the expense of increased side effects. <P> The patient needs to be involved in the management decision making in order to improve compliance with treatment. For some patients, expectant management may not be an option and they would rather have surgical treatment. Others will want to avoid surgery and will choose alternative medical options. Those who choose medical treatment need to understand that it may take days, that it can fail necessitating surgical intervention, and that it is associated with increased gastrointestinal side effects or abdominal pain. Explaining these possibilities will improve compliance with treatment. Increasing the dose of misoprostol or adding mifepristone could improve success with medical treatment.</font><p><FONT SIZE="2"><A HREF="http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11425836&dopt=Abstract">Abstract</A><P></font><CENTER><HR WIDTH=50%></CENTER><P><P><H3>American Journal of Obstetrics and Gynecology</H3><FONT SIZE="1">From</font> <FONT SIZE="3"><B><i>American Journal of Obstetrics and Gynecology</i></B></font><FONT SIZE="2"><b>August 2001 (Volume 185, Number 2)</b></font><p><h4>Evaluation of the Prognosis of in vitro Fertilization Pregnancies With Initially Low Serum Human Chorionic Gonadotropin Levels</h4> <FONT SIZE="2"> Frishman GN, Hackett RJ, McGrath M, Metheny WP<BR><i>American Journal of Obstetrics and Gynecology</i>. 2001;185(2):392-395<P></font><FONT SIZE="2"><H3>Summary</H3> <EM>Low initial serum HCG level was associated with increased early spontaneous miscarriage rate; however, if the pregnancy progressed beyond the first trimester, there was no longer an increased risk of adverse pregnancy outcome.</EM><P> This study evaluated the prognostic value of an early serum human chorionic gonadotropin (HCG) level in in vitro fertilization (IVF) pregnancies that progressed to at least 6 weeks gestation. The study is a retrospective analysis of data obtained from an IVF database and patients' charts. Only those IVF pregnancies that were singleton and intrauterine for which follow-up data were available were included. All pregnancies were supported with natural progesterone. The pregnancy was considered viable if at 6 weeks (4 weeks after HCG injection) there was an intrauterine sac and at 8 weeks a fetal heartbeat was detectable on ultrasound. <P> The first serum HCG level was obtained 14 days after the HCG injection. The doubling time of the serum HCG was evaluated as well and was considered normal if it rose at least 66% in 48 hours. Five hundred thirty-two pregnancies were identified in the IVF database. Mean HCG value was 69.8 mIU/mL 14 days after the HCG injection. A cut-off value of 20 mIU/mL was used to divide the patients into 2 groups. Group 1 comprised 65 patients who had initial HCG values &lt; 20 mIU/mL, and 130 patients formed the reference group (Group 2). They had their IVF cycles just before or after those identified in Group 1. Risk factors for spontaneous miscarriage (age, history of miscarriage, smoking, parity) were similar in the 2 groups. <P> The risk of an early miscarriage was significantly greater in Group 1 (low initial HCG, intrauterine sac at 6 weeks) [odds ratio: 5.7 (95% CI, 2.6-12.4)] At 8 weeks, there was still an increased risk in the low HCG group, but this was no longer significant (odds ratio: 2.5 [95% CI, 0.7-8.5]). If the pregnancy progressed to 13 weeks, the risk of a spontaneous miscarriage was &lt; 1% in both groups. Once a pregnancy progressed beyond 12 weeks, second- and third-trimester complications were not increased. HCG doubling times were not predictive of abnormal pregnancy outcome; most pregnancies progressed to term (Group 1: 80% of patients with abnormal doubling time, Group 2: 75% of patients with abnormal doubling time). Low initial serum HCG level was associated with increased early spontaneous miscarriage rate; if the pregnancy progressed beyond the first trimester, however, there was no longer an increased risk of adverse pregnancy outcome. <P> <h3>Clinical Commentary</h3> Certain maternal serum markers are useful for identifying abnormal pregnancies. HCG produced by the trophoblasts is one of these markers. During early pregnancy it follows a certain pattern, by doubling, or increasing by at least 66%, every 48 hours. It is well known, however, that some abnormal pregnancies follow a similar HCG pattern and normal pregnancies can be characterized by a slower HCG increase. <P> Serum progesterone is another marker that is used to identify abnormal pregnancies. While the extremes of progesterone values can provide useful information, most of the time values are in the wide gray-zone, making them less useful in clinical management. Early IVF pregnancies are supported by exogenous progesterone, so following serum progesterone values is not useful. <P> The benefit of the IVF procedure is that early serum HCG levels are available and the dating of the pregnancy is accurate. Abnormal intrauterine or extrauterine pregnancies can be identified earlier. This study evaluated the utility of measuring early HCG levels to detect pregnancies at risk for early miscarriage. Patients in both groups had similar incidence of some risk factors. We do not know whether the indication for IVF was similar in the 2 groups; nor did we know the incidence of some other important gynecologic conditions (endometriosis, PCOS, uterine abnormalities) in the 2 groups. <P> The study is a retrospective analysis. Five hundred thirty-two pregnancies were identified, but only 195 are included in the analysis. The authors do not explain why the other cases were excluded. Some must have been ectopic pregnancies; some must have ended up in a miscarriage before 6 weeks. We do not know how many cases were excluded because of incomplete data; the outcome of the study could be affected if the number is high . The authors used a cut-off of 20 mIU/ml because that is the detection minimum of most urinary assays. They could have done a receiver operating characteristic (ROC) analysis of their data to find a real discriminatory HCG value and report positive and negative predictive values associated with it. Of note is that abnormal HCG doubling time was not associated with adverse early pregnancy outcome; however, the numbers were low (17 patients out of the 195). When a low serum HCG value is obtained in an IVF setting, one has to worry about possible abnormal intrauterine gestation or ectopic gestation . This study found that low initial HCG value is associated with early spontaneous miscarriage. Measurement of serum markers can aid clinical management, but one has to rely on patients' symptoms and physical findings as well when making management decisions. It is certainly important to keep a closer eye on pregnancies with abnormal levels of serum markers.</font><p><FONT SIZE="2"><A HREF="http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11518898&dopt=Abstract">Abstract</A><P></font><CENTER><HR WIDTH=50%></CENTER><P><h4>Hormonal Contraception and Risk of Sexually Transmitted Disease Acquisition: Results From a Prospective Study</h4> <FONT SIZE="2"> Baeten JM, Nyange PM, Richardson BA, et al.<BR><i>American Journal of Obstetrics and Gynecology</i>. 2001;185(2):380-385<P></font><FONT SIZE="2"><h3>Summary</h3> <EM>This prospective study following prostitutes in Kenya found an increased risk of </EM>Chlamydia trachomatis<EM> acquisition and purulent cervicitis among oral contraceptive pill (OCP) and depot medroxyprogesterone (DMPA) users; 100% condom use reduced the risk of all sexually transmitted disease (STD) acquisition screened for.</EM> <P>This prospective cohort study evaluated the association of hormonal contraceptive methods and STDs in a group of prostitutes in Kenya. HIV-1 seronegative women were invited to participate. At the beginning of the observation period, they all had a thorough physical exam, they were screened for STDs, and they completed a questionnaire. Questions were asked about sexual behavior, contraceptive use, and condom use. They were screened for <EM>Trichomonas vaginalis </EM>infection, syphilis, <EM>Chlamydia </EM>infection, gonorrhea, and bacterial vaginosis. Those participating were asked to complete a questionnaire every month and were screened for STDs monthly. Women who used OCPs or DMPA were compared with women who did not use contraceptives or had a history of bilateral tubal ligation (BTL). Risk of STD acquisition was evaluated after adjusting for age, parity, number of sexual partners, number of sexual contacts, level of education, and condom use. <P>Of 4528 women initially screened, 2115 were HIV-1 negative; 1202 were enrolled into the cohort and provided 7877 follow-up visits. Women using DMPA had more sexual partners and sexual contacts per week. They spent more time as a prostitute before the study and were less likely to use condoms than those with a history of BTL or who did not use contraception. After controlling for risk factors for STD acquisition, OCP use was associated with an increased risk of <EM>Chlamydia</EM> infection and cervicitis with purulent discharge. Those using OCPs were also at increased risk for <EM>Candida </EM>vaginitis; they were at lower risk for bacterial vaginosis. Women using DMPA were at increased risk for <EM>Chlamydia </EM>infection and cervicitis with purulent discharge; they were at reduced risk for bacterial vaginosis, <EM>Trichomonas vaginalis</EM> infection and pelvic inflammatory disease (PID). One hundred percent condom use was associated with a reduced risk for all STDs. <P> <h3>Clinical Commentary</h3> STDs that lead to upper genital tract infection compromise the individual's future health. Women with a history of PID are more likely to complain about chronic pelvic and abdominal pain. They are also at a substantial risk for infertility. Barrier methods, if used with every sexual contact, are known to reduce the risk of STD transmission. It is thought that hormonal contraceptive methods that reduce menstrual flow will also lead to reduced risk of STD-related infections. Women who use OCPs or DMPA are less likely to use barrier methods, however. <P> This study evaluated the risk of STD acquisition in a high-risk population. The study population was followed prospectively and data were collected prospectively as well. During the analysis, the authors adjusted for known risk factors of STD acquisition, but other unidentified risk factors could have remained unbalanced between the study groups. Hormonal contraception is associated with increased cervical ectopy, leading to increased risk for <EM>Chlamydia</EM> infection. Controlling for the presence of ectopy did not change the study's findings. <P> An important finding is that consistent condom use was associated with reduced risk of STD acquisition and reduced incidence of upper genital tract infection. Reduced menstrual flow with hormonal contraceptive methods can reduce the chance for microorganisms to ascend into the upper genital tract. However, hormonal methods can also induce changes in the local environment or in the natural immunologic defense that are protective against STD acquisition. Hormonal methods provide numerous noncontraceptive health benefits as well. They do not protect against STDs, however. If one is engaged in a high-risk sexual relationship, barrier methods are needed to prevent STD transmission. This study evaluated prostitutes, so the findings are of limited value when trying to draw conclusions for the general population. Studies are needed to determine whether hormonal methods induce local vaginal, cervical changes conducive to the survival of microorganisms responsible for STDs.</font><p><FONT SIZE="2"><A HREF="http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11518896&dopt=Abstract">Abstract</A><P></font><CENTER><HR WIDTH=50%></CENTER><P><FONT SIZE="1">From</font> <FONT SIZE="3"><B><i>American Journal of Obstetrics and Gynecology</i></B></font><FONT SIZE="2"><b>July 2001 (Volume 185, Number 1)</b></font><p><h4>Hormonal and Barrier Contraception and Risk of Upper Genital Tract Disease in the PID Evaluation and Clinical Health (PEACH) Study</h4> <FONT SIZE="2"> Ness RB, Soper DE, Holley RL, et al.<BR><i>American Journal of Obstetrics and Gynecology</i>. 2001;185(1):121-127<P></font><FONT SIZE="2"><h3>Summary</h3> <EM>This study found no protective effect of any contraceptive method against upper genital tract infection. Inconsistent condom use was associated with increased risk of upper genital tract infection. </EM><P> The PEACH study was a prospective trial comparing inpatient vs outpatient treatment of PID. This report focuses on the association between contraceptive methods and pelvic infections in the study population. This multicenter trial recruited women of reproductive age with clinically suspected PID from emergency rooms and clinics. Potential candidates who were pregnant, took antibiotics, had a history of hysterectomy, underwent gynecologic surgery within 2 weeks, were considered unreliable, or who had allergy to the study medications were not enrolled. Of 2941 potential candidates identified, 1515 were considered eligible; 864 agreed to participate. <P> Before randomization to treatment, all participants were interviewed and asked about contraceptive use and sexual habits. Upper genital tract infection (UGI) was diagnosed by endometrial biopsies. All patients had a thorough physical exam, including a pelvic exam to establish the diagnosis of PID. Women with UGI were compared with women who did not have UGI. Women with UGI were younger, had lower level of education, and had more sexual partners. More black women had UGI than did women of other ethnic/racial groups.<P> Inconsistent condom use (odds ratio: 2.3 [95% CI: 1.3-4.2]) and no contraceptive method (when compared with any contraceptive method) (odds ratio: 1.7 [95% CI: 1.0-2.8]) were associated with an increased risk of UGI. The use of OCPs or MPA was not associated with UGI. There was a trend for lower incidence of UGI with consistent condom use when compared with no contraceptive use. After adjusting for age, race, level of education, toxic habits, other methods of contraception, and new partner, none of the methods were independently protective against UGI. This study found no protective effect of any contraceptive method against UGI. Inconsistent condom use was associated with increased risk of UGI. <P> <h3>Clinical Commentary</h3> This study reports data on those participants who had an endometrial biopsy to assess the presence of UGI. This is not a routinely used method for assessment of UGI and cannot necessarily be used to make a diagnosis of PID. The gold standard to establish PID is laparoscopy; however, in everyday practice the diagnosis is made on the basis of symptoms and physical findings. The opposite is true as well; women with no evidence of infection on endometrial biopsy could have PID. This means that both those diagnosed with PID and those not diagnosed with PID could have been incorrectly identified. In addition, only about one third of eligible patients had endometrial biopsies. It is not known how information on the other two thirds could have changed the findings of this study. <P> In the analysis, the authors tried to control for confounding variables; however, important risk factors were not identified, such as number of partners, presence of cervical ectopy, or other possible risk factors. Consistent condom use was not protective against UGI. This differs from findings of other studies. The relatively low number of patients with consistent condom use can be responsible for this finding. Hormonal contraceptives are thought to be protective against PID by reducing menstrual blood loss. They also increase the presence of cervical ectopy, which leads to increased susceptibility for <EM>Chlamydia </EM>infection. <P> Results with regard to the protective effects of OCP use against PID are conflicting. Women who choose hormonal methods are less likely to use barrier methods. The authors of this report controlled for other methods of contraception in their analysis. The effect on the risk of STDs and PID is just one aspect of contraceptive use. Hormonal contraceptive methods are associated with numerous health benefits. Future studies will have to further analyze the association between contraceptive methods and STDs and PID as well as the local effects of hormonal methods that can affect the transmission of such diseases.</font><p><FONT SIZE="2"><A HREF="http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11483915&dopt=Abstract">Abstract</A><P></font><CENTER><HR WIDTH=50%></CENTER><P><P><H3>Fertility and Sterility</H3><FONT SIZE="1">From</font> <FONT SIZE="3"><B><i>Fertility and Sterility</i></B></font><FONT SIZE="2"><b>September 2001 (Volume 76, Number 3)</b></font><p><h4>A Randomized, Controlled Trial of a Low-Dose Contraceptive Containing 20 microg of Ethinyl Estradiol and 100 microg of Levonorgestrel for Acne Treatment</h4> <FONT SIZE="2"> Thiboutot D, Archer DF, Lemay A, Washenik K, Roberts J, Harrison DD<BR><i>Fertility and Sterility</i>. 2001;76(3):461-468<P></font><FONT SIZE="2"><h3>Summary</h3> The administration of low-dose OCPs containing 20 mcg of ethinyl estradiol and 100 mcg levonorgestrel (LNG) is an effective and safe treatment of moderate acne vulgaris. <P> This randomized, multicenter, double-blind, placebo-controlled trial evaluated a low-dose OCP containing 20 mcg of ethinyl estradiol (E2) and 100 mcg LNG for the treatment of moderate acne. Women of reproductive age (&gt; 14 years of age) with regular menstrual cycles and moderate facial acne vulgaris were invited to participate. Potential candidates with recent hormonal therapy, acne therapy, or contraindication to OCP use were excluded. <P> Moderate acne was defined as the presence of 6-200 total facial lesions, 10-75 inflammatory lesions, and &lt; 5 nodules. Participants were evaluated for lesions at baseline and then monthly. Self-assessment was done at baseline and during cycles 4 and 6. Clinician's global assessment was carried out monthly. Evaluations were done between days 17 and 24 in each cycle. Three hundred fifty patients were randomized to receive either 20 mcg of E2 and 100 mcg LNG or placebo; 226 patients completed the study. The main reason for discontinuation of treatment was that patients were "lost to follow-up." There were no differences between the 2 groups with regard to the reason for discontinuation. Two hundred one patients who completed the study without protocol violation are included in the efficacy analysis. Results are reported based on intention-to-treat. <P> Women in the placebo group were older, but there were no differences in baseline acne score, menstrual history, body weight, or past hormone use. By the end of the study period, the numbers of inflammatory and noninflammatory lesions were reduced in both groups, as was the number of total lesions. The reduction was significantly greater for all the outcome parameters in the active treatment group. This difference was evident by cycle 2. There was no change in the number of nodules, but the numbers were very low even at baseline. The clinician's global assessment showed significant improvement in 58% of women in the active treatment group and 47% in the placebo group. Patients' self-assessment showed significantly higher rate of acne improvement in the active treatment group (80% vs 63%). Menstrual irregularities were more frequent in the active treatment group; other side effects were similar in the 2 groups. In conclusion, low-dose OCP containing 20 mcg of ethinyl estradiol and 100 mcg LNG is an effective and safe method for the treatment of moderate acne vulgaris. <P> <h3>Clinical Commentary</h3> Acne vulgaris is a common finding among women of reproductive age. It is characterized by increased sebum production, bacterial colonization, and inflammation. Sebum production is androgen dependent. Androgens originate from the ovaries and adrenal glands. The severity of symptoms is cycle dependent and worsens in the luteal phase. Progesterone, produced in higher quantities in the luteal phase, binds to progesterone and androgen receptors as well. Treatment that leads to a decrease in bioavailable androgens leads to improvement. OCPs promote decreased ovarian androgen production and increased sex-hormone binding globulin levels. The sum effect is a decrease in bioavailable androgens. <P> This study enrolled patients with moderate acne. Serum androgen levels are reported neither prior to nor after treatment. The patients were also not evaluated for possible adrenal androgen excess, such as late-onset congenital adrenal hyperplasia. Acne assessment was objective, and evaluating physicians and patients were blinded to treatment. The study design is excellent. Evaluations were done in similar phases of the menstrual cycle accounting for cyclic changes. The authors report data based on intention-to-treat and based on the efficacy population. For the most part, findings do not differ. While there was impressive improvement, both objective and subjective, with the placebo as well, improvement was always greater with the active treatment. This could be explained by improved skin hygiene during the study or could reflect the natural intermittent characteristics of the skin condition. <P> Previous reports already showed beneficial effects of OCP in the treatment of acne, but those preparations contained higher amounts of steroids. This study evaluated the effects of one of the newer preparations containing low-dose steroids. Low-dose OCPs have similar beneficial effects to the higher-dose OCPs. They could be offered to women with acne; however, their use should be combined with topical skin care and anti-inflammatory antibiotic treatment.</font><p><FONT SIZE="2"><A HREF="http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11532465&dopt=Abstract">Abstract</A><P></font><CENTER><HR WIDTH=50%></CENTER><P><P><H3>Acta Obstetrica et Gynecologica Scandinavica</H3><FONT SIZE="1">From</font> <FONT SIZE="3"><B><i>Acta Obstetrica et Gynecologica Scandinavica</i></B></font><FONT SIZE="2"><b>September 2001 (Volume 80, Number 9)</b></font><p><h4>Transvaginal Ultrasonography and Hysteroscopy in Postmenopausal Bleeding - A Prospective Study</h4> <FONT SIZE="2"> Sousa R, Silvestre M, Almeida E, et al.<BR><i>Acta Obstetrica et Gynecologica Scandinavica</i>. 2001;80(9):856-862<P></font><FONT SIZE="2"><h3>Summary</h3> <EM>No endometrial cancer was found on ultrasound when the endometrium was thinner than 4mm. When the endometrium was thicker, hysteroscopy was superior to ultrasound in detecting endometrial cancer but still did not detect all cancer cases. </EM><P> Postmenopausal bleeding is a common gynecologic complaint and could be a sign of endometrial cancer. There are several invasive and noninvasive diagnostic tests available to assess the endometrium for abnormalities. This prospective study evaluated transvaginal sonography and hysteroscopy in the evaluation of postmenopausal bleeding and compared results with pathology findings. Menopausal patients with bleeding were recruited. Data were collected for medical problems, use of anticoagulants, and use of hormone replacement therapy (HRT). All participants were evaluated with transvaginal ultrasound, followed by hysteroscopy. Surgeons were blinded to ultrasound findings. <P> Ultrasound findings were described as normal, focal abnormality (benign or suspicious), or diffuse abnormality (benign or suspicious). Hysteroscopic findings were described similarly. After the hysteroscopy, directed or random endometrial biopsy was performed and evaluated for pathology. Eighty-eight patients were enrolled; 69 completed all tests. Hysteroscopy could not be carried out in 15 patients, and 4 patients withdrew from the study. The average age of the participants was 62.1 years. The average time since menopause was 12.7 years. HRT was used by 18.8% of participants, 36.2% of participants had hypertension, and 11.6% had diabetes. <P> Ultrasound assessment suggested that focal suspicious lesions were present in 4.3% of the cases and diffuse suspicious abnormalities were present in 11.6% of the cases. Hysteroscopy revealed suspicious focal abnormality in 10.1% of the cases and suspicious diffuse abnormality in 2.9% of the cases. Ultrasound was a poor test to differentiate between diffuse and focal lesions. Tissue sample was obtained by directed biopsy in 20% of cases and by Novak curettage in the others. <P> Histologic exam revealed polyps in 12 cases, simple hyperplasia in 3 cases, atypical hyperplasia in 1 case, and endometrial cancer in 9 cases. Thirty-nine women had operative procedures. The main differences between biopsy and operative pathology results concerned focal lesions. Women with endometrial cancer were found to have thicker endometria on ultrasound, with a mean thickness of 21.4 mm. In all cases, endometrial thickness was greater than 8 mm when the diagnosis of cancer was made. Ultrasound had a sensitivity of 77.8%, a specificity of 93.3%, a positive predictive value of 63.6%, and a negative predictive value of 96.6% for detecting endometrial cancer. Hysteroscopy had a sensitivity of 88.9%, a specificity of 98.3%, a positive predictive value of 88.9%, and a negative predictive value of 98.3%. The combination of both tests had a sensitivity of 100%, a specificity of 91.7%, a positive predictive value of 64.3%, and a negative predictive value of 100% for detecting endometrial cancer. <P> In conclusion, no endometrial cancer was found when the endometrium was thinner than 4 mm on ultrasound. When the endometrium was thicker, hysteroscopy was superior to ultrasound in detecting endometrial cancer but still did not detect all cancer cases. <P> <h3>Clinical Commentary</h3> Postmenopausal bleeding is a common gynecologic condition. Most of the bleeding episodes are associated with benign findings, such as atrophy, or with benign focal lesions, such as polyps; however, the presence of cancer needs to be ruled out. Although cancer is an infrequent finding with postmenopausal bleeding, most cancers will present with bleeding. <P> There are several invasive and noninvasive methods that can be used to evaluate the endometrium. Ultrasound has been used for a long time to assess the uterine lining, and various endometrial thickness criteria were established to differentiate normal from abnormal findings. Most studies use a cut-off value of 4 or 5 mm for women not using HRT and 8 mm for women taking HRT. When the thickness is below these cut-off values, it is very unusual to find cancer, but a lining that is thicker typically has a poor positive predictive value for detecting cancer. <P> Saline infusion during ultrasound evaluation improves the detection rate of focal lesions but was not evaluated in this study. Hysteroscopy allows direct visualization of the endometrial lining. It leads to improved detection of focal lesions that may show up as endometrial thickness on ultrasound. The use of hysteroscopy also allows directed biopsy of suspicious areas. Unfortunately, it could be impossible to perform a hysteroscopy in postmenopausal women who have genital tract atrophy. <P> Tissue sample for pathologic examination can be obtained by random or directed biopsy or by dilatation and curettage. Outpatient biopsies correlate well with findings during curettage but can miss the abnormal areas. False-negative results can be reduced by the use of directed biopsies. This study evaluated postmenopausal women with bleeding. Twenty percent of participants needed to be excluded mainly because hysteroscopy could not be performed. These cases were excluded from the analysis. Had they been included in the analysis as inconclusive findings, the results of this study would have been poorer. Hysteroscopy was associated with good sensitivity and specificity in the assessment of endometrial cancer but still missed 1 of the 9 cancer cases. <P> It is unusual to find cancer when the endometrium is thin on ultrasound. When the endometrium is thicker, hysteroscopy can differentiate focal lesions from diffuse endometrial abnormalities and allow directed biopsies to be obtained. Because hysteroscopy can be done in the office, the need for dilatation and curettage done under general anesthesia in an operating room can be reduced. It is important to evaluate the endometrial cavity thoroughly to rule out the presence of cancer. To achieve an accurate diagnosis, one has to obtain tissue for pathologic examination, especially when the lining is thick.</font><p><FONT SIZE="2"><A HREF="http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11531638&dopt=Abstract">Abstract</A><P></font><CENTER><HR WIDTH=50%></CENTER><P><FONT SIZE="1">From</font> <FONT SIZE="3"><B><i>Acta Obstetrica et Gynecologica Scandinavica</i></B></font><FONT SIZE="2"><b>August 2001 (Volume 80, Number 8)</b></font><p><h4>Clinical and Pregnancy Outcome Following Ectopic Pregnancy; A Prospective Study Comparing Expectancy, Surgery and Systemic Methotrexate Treatment</h4> <FONT SIZE="2"> Oloffson JI, Sundstrom I, Ottander U, Kjellberg L, Damber MG<BR><i>Acta Obstetrica et Gynecologica Scandinavica</i>. 2001;80(8):744-749<P></font><FONT SIZE="2"><h3>Summary</h3> <EM>Methotrexate treatment is a safe and effective alternative to surgical treatment for well-selected patients with unruptured ectopic gestation.</EM><P> This prospective study evaluated clinical and pregnancy outcome after conservative medical or surgical management of ectopic gestation. Patients with suspicion for ectopic gestation were enrolled over a period of 3 years. Diagnosis of ectopic pregnancy was made on the basis of serum beta human chorionic gonadotropin (betaHCG) levels and ultrasonographic findings. The diagnosis was made if the betaHCG level was &gt; 1800 IU/L and no viable intrauterine pregnancy was seen on ultrasound or if the betaHCG level was &lt; 1800 IU/L but did not rise by at least 50% in 48 hours. If the betaHCG was &lt; 1800 IU/L and was declining, it was considered to be consistent with spontaneous abortion or spontaneously absorbing ectopic pregnancy. <P> Patients who were clinically and hemodynamically stable, had normal values for standard laboratory tests, had betaHCG levels &lt; 7500 IU/L, and had ectopic gestations smaller than 35 mm on ultrasound were eligible for the study. They were treated with methotrexate (MTX), conservative surgery (salpingostomy, salpingotomy), or expectant management. Treatment assignment was not randomized. <P> The dose of MTX was 50 mg/m². BetaHCG was repeated on days 4 and 7 after MTX. If the level dropped by 15%, weekly serum betaHCG determinations were performed until it reached &lt; 10 IU/L. If the level reached a plateau, a repeat injection was administered. Eighty-nine eligible patients were enrolled; 26 were treated with MTX, 46 surgically and 17 expectantly. Baseline characteristics were similar, except that more advanced gestation and significantly higher betaHCG levels were seen in the surgery group. Treatment was successful in 77% of MTX patients and in 83% of the patients managed expectantly. Six MTX patients were treated surgically, 1 secondary to no response to MTX and 5 secondary to worsening clinical symptoms. Of those who wanted to conceive after treatment, 64% in the MTX group, 51% in the surgery group, and 31% in the expectant management group did so. No major side effects occurred during MTX treatment. MTX is a safe and effective alternative to surgical treatment for well-selected patients with unruptured ectopic gestation.<P> <h3>Clinical Commentary</h3> A small percentage of pregnancies -- 1% to 2% -- are ectopic pregnancies. Before we had sensitive serum assays and readily available ultrasound, these pregnancies progressed to the point where they ruptured and needed to be treated surgically. Now we are able to diagnose them early, before they rupture. The availability of early diagnosis has led to the development of conservative surgical and medical management options. When the fallopian tube is not ruptured, one can attempt to open it up and "milk" the pregnancy out, saving the tube. The latest option is medical management, using MTX. <P> This study assessed clinical response to these conservative methods and subsequent pregnancy rates. Unfortunately, patients were not randomized to treatment, and there were some differences between the patients in the 3 groups. Patients in the surgery group had more advanced gestations and higher betaHCG levels. It is known from previous studies that the higher the betaHCG level, the more likely that MTX treatment will fail. It seems that the more advanced ectopic pregnancies were treated surgically and the smaller ectopic pregnancies that were more likely to respond to medical treatment were treated with MTX. Toxic side effects are very rare with a single dose of MTX, and this was confirmed by this study. <P> The goal of conservative management is to maintain the possibility of unassisted future pregnancy. During the follow-up period in this study, two thirds of patients treated with MTX achieved pregnancy. A similar proportion of patients treated surgically achieved pregnancy as well. It is not clear, though, whether these patients used assisted reproductive technologies to achieve pregnancy. The reason for failure in the remaining patients is also not known, because tubal patency was not evaluated. They could have been infertile because of other problems. <P> This study reports a relatively low success rate with MTX. Because the investigators report findings from the first few years of their experience with MTX, it is possible that they had a low threshold for intervention if the patients had worsening conditions. It is well known that many patients complain of worsening abdominal pain in the first few days after MTX injection. It is important to select patients carefully for MTX treatment and to counsel them about the possible side effects in order to increase compliance and success with this method of treatment of unruptured ectopic gestation.</font><p><FONT SIZE="2"><A HREF="http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11531618&dopt=Abstract">Abstract</A><P></font><CENTER><HR WIDTH=50%></CENTER><P><P><H3>JAMA</H3><FONT SIZE="1">From</font> <FONT SIZE="3"><B><i>JAMA</i></B></font><FONT SIZE="2"><b>September 26, 2001 (Volume 286, Number 12)</b></font><p><h4>Endocrine Function and Oocyte Retrieval After Autologous Transplantation of Ovarian Cortical Strips to the Forearm</h4> <FONT SIZE="2"> Oktay K, Economos K, Kan M, Ruckinski J, Veeck L, Rosenwaks Z<BR><i>JAMA</i>. 2001;286(12):1490-1493<P></font><FONT SIZE="2"><h3>Summary</h3> <EM>This is a report of 2 cases of hormone production that occurred after transplantation of ovarian cortical tissue to the forearm. In 1 of the cases, oocyte retrieval was performed but fertilization was not achieved.</EM><P> Intact ovarian function is necessary for the production of the steroid hormones estradiol and progesterone and for the cyclic release of oocytes. Radiation therapy, chemotherapy, or surgical removal of the ovaries can compromise ovarian function. If ovarian function is damaged as a result of such intervention, women need to start HRT, and they face infertility. This paper reports 2 cases in which ovarian tissue was removed before such an intervention and was transplanted to the forearm. Endocrine function of these transplants was assessed. <P> The first patient was diagnosed with cervical cancer and was instructed to undergo chemotherapy and pelvic radiation therapy. Before chemotherapy and radiation therapy, both ovaries were removed and assessed for metastasis. Once frozen section ruled out the presence of metastasis, cortical strips were prepared and transplanted to the forearm. Estradiol replacement was started after the surgery. The arm was shielded during postoperative radiation therapy. After the operation, gonadotropin levels rose to the menopausal range. Ten weeks after surgery, follicle development was identified on ultrasound. Estrogen replacement was discontinued, and estradiol production in the transplanted ovarian tissue was shown; gonadotropin levels returned to the normal reproductive range. Extended monitoring revealed estradiol surges consistent with cyclic function, but ovulatory progesterone levels were not documented. <P> An immature oocyte was retrieved during the "natural cycle." After stimulation of ovarian tissue with exogenous gonadotropins, 2 postmature oocytes and 1 immature oocyte were retrieved. Injection of the immature oocyte did not lead to fertilization. The patient's FSH level was in the normal range 18 months after surgery. <P> The second patient underwent oophorectomy because of recurrent benign ovarian cysts. The other ovary had been previously removed for a benign cyst. Healthy ovarian cortical strips were transplanted to the forearm. Postoperative gonadotropin levels rose to the postmenopausal range, and the patient was started on HRT. One month after the surgery, follicle development was observed on ultrasound, and hormone production was demonstrated. HRT was discontinued. The patient had a spontaneous menstrual period. Gonadotropin levels decreased to the normal reproductive age range. Cyclic hormone production continued, followed by cyclic spontaneous menstruation.<P> <h3>Clinical Commentary</h3> The ovaries serve a dual purpose. They produce steroid hormones, estradiol, and progesterone in a cyclic fashion; these hormones are necessary to maintain health. The ovaries are also the anatomic location of the oocytes; in a cyclic fashion, a cohort of oocytes is recruited and one of them is released during ovulation. The ovaries are sensitive to certain toxic effects, such as chemotherapy (mainly alkylating agents) and radiation therapy. Ovarian function can also be compromised during pelvic/adnexal surgery and during uterine artery embolization procedure. In unusual cases, the damage is transient and ovarian function returns. If damage is permanent, the patients face infertility and the risks of hypoestrogenism. Before intervention, if time allows, patients can undergo in vitro fertilization with embryo freezing for future transfers. This can address the issue of infertility but does not address hypoestrogenism. <P> Freezing human oocytes has been unsuccessful so far. The ovaries can be laterally transpositioned before pelvic radiation, however scatter radiation can still compromise their function. Alternatively, ovarian tissue can be removed and transplanted to safe sites. One of the risks of autotransplantation is the possibility of transplanting tissue that has microscopic metastasis not detected on frozen tissue exam. The tissue can be transplanted fresh or frozen-thawed. This study showed that once adequate blood supply develops the transplanted tissue can regain its capacity for steroidogenesis and follicle development. Only one of the patients tried to undergo stimulation of this ovarian tissue to undergo IVF. Mature oocytes were not retrieved and fertilization was not achieved. It is not known how the transient loss of adequate blood supply affects oocyte quality. If IVF with embryo freezing is not possible before radiation or chemotherapy, this is a promising alternative for those who need such intervention. It is also important that physiologic hormone production can be restored avoiding the risks of hypoestrogenism.</font><p><FONT SIZE="2"><A HREF="http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11572742&dopt=Abstract">Abstract</A><P></font><CENTER><HR WIDTH=50%></CENTER><P><P><H3>Journal of Clinical Endocrinology and Metabolism</H3><FONT SIZE="1">From</font> <FONT SIZE="3"><B><i>Journal of Clinical Endocrinology and Metabolism</i></B></font><FONT SIZE="2"><b>September 2001 (Volume 86, Number 9)</b></font><p><h4>Long-term Ovarian Function Evaluation After Autografting by Implantation With Fresh and Frozen-Thawed Human Ovarian Tissue</h4> <FONT SIZE="2"> Callejo J, Salvador C, Miralles A, Vilaseca S, Lailla JM, Balasch J<BR><i>Journal of Clinical Endocrinology and Metabolism</i>. 2001;86(9):4489-4494<P></font><FONT SIZE="2"><h3>Summary</h3> <EM>This study showed that ovarian cortical tissue grafted to the forearm or the abdominal rectus muscle can transiently regain its hormone-producing capacity and in rare cases can lead to follicle development.</EM><P> This is another study evaluating the long-term endocrine changes following ovarian tissue autografting to various anatomic locations. Premenopausal women undergoing hysterectomy with removal of the adnexa were invited to participate. Fourteen women were recruited; 4 underwent autografting, the remaining 10 served as controls. All participants had BMI &lt; 30 kg/m², normal baseline estradiol and follicle stimulating hormone (FSH) levels, and regular menstrual cycles. The age range was 46-49 years. The 4 patients who underwent autografting had benign indications for their initial surgery. Two patients had fresh intact ovarian cortical tissue transplanted to the forearm. One patient had fresh minced ovarian cortical tissue transplanted into the rectus muscle and 1 patient underwent transplantation of ovarian cortical tissue after 3 months of cryopreservation. <P> All participants had endocrine testing within a month before their surgery and were tested again 4-5 weeks after surgery. The experimental subjects were tested 8-10 days after surgery and then monthly up to 1 year afterwards. After the hysterectomy and oophorectomy, estradiol levels dropped and gonadotropin levels rose to the postmenopausal range in all participants. In the 2 patients who had ovarian tissue transplanted into the forearm, hormone production resumed 3-4 months after the surgery and was maintained for 2-4 months. There was no evidence of dominant follicle or corpus luteum formation on ultrasound. One of the patients who had the ovarian tissue transplanted into the rectus muscle showed no evidence of hormone production during the 1-year follow-up. The patient who had the cryopreserved-thawed, minced ovarian tissue grafted into the rectus muscle showed evidence of hormone production 3-4 months after the surgery. In this patient, there was evidence of dominant follicle formation and human chorionic gonadotropin injection, which led to luteinization of this follicle. Hormone production was maintained for 5-6 months. <P> Despite increased estradiol production in 3 out of 4 experimental subjects, FSH levels remained high, in the 20-30 IU/L range. This study showed that ovarian cortical tissue grafted to the forearm or the abdominal rectus muscle can transiently regain its hormone-producing capacity and, in rare cases, can lead to follicle development.<P> <H3>Clinical Commentary</H3> This is another study evaluating ovarian autotransplantation, but it differs from the previous one in that the participants are volunteers, women who have completed childbearing and are in their perimenopausal years. The age range is 46-49 years. This is important since the endocrine function of the ovary changes during the years of transition, from normal reproductive function into menopause. Unusual endocrine findings, such as increased or decreased estradiol production and/or anovulatory cycles, are common. <P><P> When an ovary is removed and is transplanted into a different location, one would expect even more of these unusual endocrine patterns. The process of removal and grafting (and the freeze-thaw process if not grafted fresh) will add hypoxic damage to an ovary that already has no great reserve. So the findings of this study (no hormone production in 1 case and transient hormone production in the others) should not be considered discouraging. Ovarian tissue transplantation is a procedure aimed at helping younger women who need to undergo a procedure that could compromise future ovarian function. Successful grafting gives them the benefit of cyclic hormone production and a hope for reproduction. Another important finding of this study is that the ideal site of transplantation is not yet known. Ovarian function was shown at both anatomic locations, but better blood supply in the rectus muscle could be a better site for grafts. The question was raised as to what kind of tissue should be grafted, intact or minced. The authors hypothesize that minced tissue suffers less hypoxic damage because of faster development of blood supply. Further studies need to address these issues.</font><p><FONT SIZE="2"><A HREF="http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11549698&dopt=Abstract">Abstract</A><P></font><CENTER><HR WIDTH=50%></CENTER><P><P>