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Adenomyosis is a benign disease whose symptoms mimic those of uterine leiomyoma. Hysterectomy is the treatment of choice; conservative surgery is difficult to perform and can damage the uterine structural integrity. We report the case of a 36-year-old woman who had difficulty conceiving because of profuse menometrorrhagia. An 84 cm3 uterine tumour was diagnosed on ultrasonography as leiomyoma, and conservative myomectomy was planned. Magnetic resonance imaging (MRI) corrected the diagnosis to focal adenomyosis. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) destroyed a significant part of the tumour. Following an uncomplicated MRgFUS treatment, a non-perfused volume of 33 cm3 was measured. At 6 weeks, the patient experienced a significant reduction in menometrorrhagia and a marked decrease in tumour size (about 50%). She conceived spontaneously and, after an uneventful pregnancy, gave birth at term to a healthy infant via normal vaginal delivery. No structural uterine abnormality was detected after her delivery. This report highlights the difficult diagnosis and new therapeutic considerations of adenomyosis. MRgFUS seems to have the potential to precisely and effectively treat focal adenomyosis without damage to surrounding healthy myometrium, allowing for normal reproduction. Further studies are needed to assess the overall safety and long-term effectiveness of MRgFUS for the non-invasive treatment of adenomyosis. [ABSTRACT FROM AUTHOR]

BACKGROUND Chemotherapy destroys primordial follicles and can lead to ovarian atrophy. Although reports indicate that apoptosis is the mechanism responsible for follicle loss, additional pathways can be involved. This study investigates the damage in human ovaries after administration of non-sterilizing doses of chemotherapy. METHODS In a blind study, pathological changes in ovarian tissue harvested for cryopreservation were evaluated. The study group comprised young non-sterile cancer patients, previously exposed to chemotherapy who were (mean ± SD), when compared with non-exposed patients. RESULTS Thirty-five cancer patients aged 28.7 ± 6.74; 17 were previously exposed to non-sterilizing chemotherapy and 18 were not. In all samples, primordial follicles were present. In previously exposed patients, damage to cortical blood vessel and proliferation of small vessels was observed. The cortex showed focal areas of fibrosis with disappearance of follicles (sensitivity 76%, positive predictive value 75% for CONCLUSIONS Injury to blood vessels and focal ovarian cortical fibrosis are aspects of ovarian damage caused by chemotherapy. These findings indicate a potential additional mechanism of damage to the direct apoptotic effect of chemotherapy on follicles. The possibility that these changes are involved in ageing ovaries should be further investigated. [ABSTRACT FROM AUTHOR]

Purpose: To assess the long-term outcomes of MR-guided focused ultrasound (MRgFUS) for treating uterine fibroids, focusing on re-intervention rates, pregnancy outcomes, and the onset of menopause over a 7-year follow-up period., Materials and Methods: We conducted a historical cohort study of 99 women with symptomatic uterine fibroids who underwent MRgFUS between 2013 and 2020 at a single tertiary medical center. Data collection included patient demographics, treatment details, and follow-up interviews. Re-intervention rates were evaluated using Kaplan-Meier curves and Cox regression analysis to identify predictors of further treatments, with a specific focus on age-related differences., Results: Over a median follow-up of 6.1 years, 33.1% of women required re-intervention for persistent fibroid symptoms. The median patient's age was 43 years old. Women aged ≤ 43 years had significantly higher re-intervention rates than those aged 44 + years (47.5% vs. 16.7%, p = 0.005). Multivariable Cox regression identified age as the sole significant predictor of re-intervention (HR 44+vs. <43 0.303 95% CI 0.128-0.714, p = 0.006). Sixteen women conceived after MRgFUS, resulting in 21 pregnancies, with 72.2% live births and a spontaneous miscarriage rate of 22.2%. The mean age of menopause was 51.4 years, similar to global averages., Conclusions: MRgFUS is a practical, noninvasive option for treating symptomatic uterine fibroids. Older women show lower re-intervention rates. Pregnancies post-MRgFUS are possible, and the procedure does not appear to affect the onset of menopause. Age remains a crucial predictor for further re-intervention., (© 2025. The Author(s).)

Key Message: Menstruation of adolescent girls might be influenced by Covid-19 mRNA vaccine, however, the ovarian reserve estimated by AMH is not compromised., Background: Recent studies have suggested that the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine causes menstrual abnormalities which led to concerns regarding its influence on the reproductive system. This study aims to investigate the influence of the SARS-CoV-2 mRNA vaccine on gynecologic well-being and future fertility of adolescent girls., Methods: This is a prospective cohort study conducted at a university affiliated medical center between June and July 2021. Adolescent girls aged 12-16 years who were vaccinated by two Pfizer-BioNTech Covid-19 vaccines (21 days apart) were included in the study. All participants completed a computerized questionnaire regarding their general medical and gynecological background at recruitment and 3 months later. Blood samples were collected for AMH levels before and 3 months following the first mRNA vaccine RESULTS: The study group consisted of 35 girls, and of them, follow-up was completed by questionnaire and AMH sampling in 35 (90%) and 22 (56%) girls, respectively. Among the 22/35 girls who reported regular menstruation before vaccination, seven (31.8%) experienced irregularities post-vaccination. Four of the eight pre-menarche girls included in the study reported on menarche on follow-up. Median AMH levels were 3.09 (IQR 1.96-4.82) μg/L and 2.96 (2.21-4.73) μg/L at baseline and after 3 months, respectively (p = 0.07). After controlling for age, BMI and presentation of side effects, no association was demonstrated to the change in AMH levels (AMH2-AMH1)., Conclusions: Although menstruation of adolescent girls might be influenced by Covid-19 mRNA vaccine, it seems that the ovarian reserve estimated by AMH is not compromised., Clinical Trial Registration: National Institutes of Health (NCT04748172)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: MRI guided focused ultrasound (MRgFUS) is a noninvasive technique for treating uterine fibroids. The presence of abdominal scars can limit the number of women eligible for the procedure, due to absorbance of beam energy. The goals of this study were to assess the number of women that fit the procedure and to compare outcomes among women with or without abdominal scars., Material and Methods: A prospective cohort study of all women that were interested in MRgFUS in a single University-Affiliated Hospital between November 2012 and December 2019. Rates of women that were referred to further screening, fulfilled selection criteria and underwent the procedure were compared between patients with or without abdominal scars. We evaluated the treatment parameters of the two groups and used linear regression model predict non-perfused volume (NPV) at the end of the process., Results: Out of 701 patients, 21.8% were suitable for MRgFUS. Women with scars had significant lower NPV compared with women without scars (60% versus 82.4%, p  = 0.021). No serious adverse events were reported in both groups. Linear regression models showed that fibroids' volume, stopping the treatment due to severe pain and the presence of abdominal scars had a statistically significantly negative effect on NPV (betas: -11.51, -6.96, and -6.29, p -values: <0.001, 0.003, and 0.007 respectively), while number of sonication had a statistically significantly positive effect on NPV (beta = 5.98, p  = 0.011)., Conclusion: Regardless of strict inclusion criteria, MRgFUS treatment is less efficient among women with abdominal scars, although still feasible for those who are interested in noninvasive option.

Objective: Opposite-sex twins have shown behavioural and reproductive differences between females and males. These differences may be determined by higher intrauterine levels of androgens among females that were exposed to a male co-twin. The aim of this study was to compare cord blood androgen levels in females from same-sex and opposite-sex twins., Design: A prospective study. In this pilot study, we compared cord blood androgens (DHEA-S, Δ-4 androstenedione, total testosterone-TT) and sex hormone-binding globulin (SHBG) levels in 20 females from same sex and 20 females from opposite-sex dichorionic diamniotic twins. We used generalized estimating equation (GEE) modelling to assess differences in cord blood androgens between females from same-sex twin pregnancies and females from opposite-sex twin pregnancies., Patients: Twenty opposite-sex twin pairs (female-male twins) and 20 same-sex twin pairs (female-female)., Measurements: Cord blood total testosterone, Δ-4 androstenedione, DHEA-S and sex hormone-binding globulin (SHBG) levels., Results: No difference in the levels of androgens as Δ-4 androstenedione, total testosterone and SHBG was identified between females that were exposed to a female co-twin compared with females that were exposed to a male co-twin. DHEA-S levels were significantly lower among females from opposite-sex twins compared with females from same-sex twins., Conclusions: Our preliminary data do not support the hypothesis that females exposed to male co-twins are exposed to higher levels of androgens in utero compared with females exposed to female co-twins. Further studies are needed to explain the reported behavioural and reproductive differences among opposite-sex twins., (© 2020 John Wiley & Sons Ltd.)

Background: Fibroid tumors are the most common benign tumors in women of reproductive age. Treatment is usually indicated for those who are symptomatic, with different techniques being used., Objective: The purpose of this study was to compare the long-term outcome of laparoscopic myomectomy with magnetic resonance-guided focused ultrasound for symptomatic uterine fibroid tumors., Study Design: A cohort study was conducted on all patients with symptomatic uterine fibroid tumors who were admitted to a single tertiary care center and treated operatively with laparoscopic myomectomy or treated conservatively with magnetic resonance-guided focused ultrasound from January 2012 until January 2017. Assessment for further interventions and sustained fibroid-associated symptoms was performed, with the use of the Uterine Fibroid Symptom and Quality of Life symptom severity score., Results: One hundred fifty-four women met the inclusion criteria. Complete follow-up evaluation was achieved for 64 women who underwent laparoscopic myomectomy and for 68 women who were treated by magnetic resonance-guided focused ultrasound. Follow-up time was similar for the 2 groups (median, 31 months [interquartile range, 17-51 months] vs 36 months [interquartile range, 24-41]; P=.95). The rate of additional interventions was 5 (7.8%) and 9 (13.2%), respectively (P=0.312). Similarly, the Uterine Fibroid Symptom and Quality of Life symptom severity score questionnaire score at follow-up interviews revealed comparable median scores of 17 (interquartile range, 12-21) vs 17 (interquartile range, 13-22) for laparoscopic myomectomy and magnetic resonance-guided focused ultrasound, respectively (P=.439). Analysis of each of the symptoms separately (bleeding, changes in menstruation, abdominal pain, bladder activity, nocturia, fatigue) did not change these findings, nor did a multivariate analysis., Conclusion: Satisfaction with long-term outcome and rate of reinterventions after magnetic resonance-guided focused ultrasound treatment or laparoscopic myomectomy for uterine fibroid tumors was comparable. Further larger randomized trials are needed to confirm these findings., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Intracavitary uterine fibroids and fibroids that distort the uterine cavity are associated with excessive vaginal bleeding and infertility. While intracavitary fibroids smaller than 4 cm are usually treated safely by operative hysteroscopy, larger fibroids may require multiple surgeries or more extensive surgery with possible damage to the integrity of the uterine wall. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a noninvasive approach for treating uterine fibroids, mainly the intramural type. We present the outcome of MRgFUS treatment for intracavitary fibroids (FIGO class 1) in cases that could not be treated by hysteroscopy due to either fibroid size or patient refusal. (Canadian Task Force II-1)., Study Design: A retrospective cohort study from a single tertiary referral center. A total of 68 patients were treated by MRgFUS for symptomatic uterine fibroids from January 2013 to December 2016. Six of them had FIGO class 1 fibroids. Adverse effects and short- and long-term outcomes (quality of life issues and need for additional surgical intervention) were assessed during ambulatory clinic visits and by phone interviews., Results: The mean ± SD fibroid volume on MRI screening was 86.3 ± 60.9 cm 3 . Six of those patients underwent the procedure (mean age 40.5 ± 5.6 years, range 33-48). The follow-up duration was 24.1 ± 12.0 months. Four patients were not interested in future fertility and did not undergo additional treatment, while the two who planned to conceive underwent another surgical intervention (one underwent operative hysteroscopy after reduction of fibroid size and the other underwent laparoscopic myomectomy)., Conclusion: This preliminary study shows that MRgFUS can be a feasible treatment option for FIGO class 1 uterine fibroids. Shrinkage of fibroids by MRgFUS can obviate or facilitate subsequent surgical intervention in selected cases., (Copyright © 2017. Published by Elsevier B.V.)

With the recent trend toward single embryo transfer (ET), cryopreservation of extraneous embryos is becoming increasingly prevalent. Several replacement protocols for frozen-thawed ET (FET) exist, with no advantage of one protocol over the others. All consecutive patients undergoing natural cycle Day-3 FET cycles between May 2012 and March 2015 in our IVF unit were evaluated. While following spontaneous ovulation, all patients received progesterone luteal support. Since June 2014, patients underwent the same aforementioned natural cycle FET cycles, with two additional injections, one of recombinant hCG (250 mcg) and the other of GnRH-agonist (triptorelin 0.1 mg), on the day of transfer and 4 d later, respectively. While the patients' clinical characteristics, the prevalence of embryos that survived the thawing process and the number of embryos transferred were comparable between the earlier as compared with the later period, implantation rate, positive β-hCG, clinical, and ongoing pregnancy rates were significantly higher during the later period. We, therefore, suggest that when natural cycle FET is offered, the addition of two injections of recombinant hCG and GnRH-agonist, on the day of transfer and 4 d later, respectively, might increase clinical pregancy rates. Further large prospective studies are needed to elucidate the aforementioned recommendation prior to its routine implementation.

Study Question: What are the factors associated with long-term success in patients with symptomatic uterine fibroids treated by magnetic resonance-guided focus ultrasound (MRgFUS) and can they be employed to create a clinically useful index that predicts long-term efficacy?, Summary Answer: Hypo-intense fibroids on T2-weighted magnetic resonance imaging (MRI) and older age were associated with higher success rates and can be used to predict success rates on the basis of their presence or absence as pre-treatment parameters., What Is Known Already: The signal intensity of baseline T2-weighted MRI images and non-perfused volume at the end of the treatment can be correlated with MRgFUS outcome., Study Design, Size and Duration: This was a retrospective analysis of 81 patients who were treated by MRgFUS for symptomatic uterine fibroids, in an academic affiliated center between 2003 and 2008., Participants/materials, Setting and Methods: There was a post-treatment phone interview >6 months following MRgFUS for symptomatic uterine fibroids., Main Results and the Role of Chance: The eighty-one patients completed a successful MRgFUS treatment during this period, of whom 74 were included in the final analysis (1 was post-menopausal at treatment and 5 were lost for follow-up). The mean time for the phone interview was 33.0 ± 15.1 months (range: 6-53 months) after the MRgFUS treatment. Fifty-five patients (69%) did not need any additional alternative treatment following MRgFUS. Nineteen patients (24%) underwent other surgical interventions. Hypo-intense fibroids were associated with a higher chance of success than hyper-intense fibroids [odds ratio = 2.96 (1.01-8.71); P = 0.04] for surgery in hyper-intense fibroids). Women with long-term treatment success were significantly older at the time of treatment [46.3 ± 3.8 (range: 37-53) years versus 43.6 ± 4.4 (range: 36-51) years, respectively; P = 0.02]., Limitations and Reasons for Caution: Retrospective non-comparative studies are suboptimal and might overemphasize favorable outcomes., Wider Implications of the Findings: This paper can contribute to selection of suitable candidates for the MRgFUS treatment for patients with uterine fibroids' and can serve as a guide for gynecologists for a better patient selection., Study Funding/competing Interest(s): None., Trial Registration Number: N/A.

The aim of the present study was to evaluate the possible risk for cancer development in infertile women with over 30 years of follow-up. Cancer development was assessed through linkage with the National Cancer Registry updated to 31 December 2005 in a cohort of 2431 women who were treated for infertility at the Sheba Medical Center in Israel during the period 1964-1974 and contributed more than 84,000 women years of follow-up. Standardized incidence ratios (SIR) were calculated between the observed cancer cases and the expected cancer rates in the general population. The mean age at the end of follow-up was 62.7 years. Eighteen cases of ovarian cancer were observed as compared to 18.1 expected (SIR = 1.0; 95% CI = 0.59-1.57). For breast cancer, 153 cases were observed as compared to 131.9 expected (SIR = 1.16; 95% CI = 0.98-1.36), and for endometrial cancer, 30 cases were observed as compared to 17.8 expected cases (SIR = 1.69; 95% CI = 1.14-2.41). No excess risk associated with exposure to gonadotropins was observed. Infertility was found to be associated with significant increased risk for endometrial cancer and borderline increased risk for breast cancer. Ovarian cancer risk was not found to be elevated. No significant excess risk was associated with treatment with ovulation induction.

Adverse effects have been related to infertility treatments. Infertility in general, and female infertility in particular, is a well established risk factor for cancer development, especially ovarian, breast and endometrial cancer. This article addresses the possible association between infertility and cancer development, with an emphasis on the influence of infertility treatments, through a meticulous search of the literature published thus far. While results regarding the possible association of infertility, ovulation induction medications and invasive ovarian cancer show no increased risk and are reassuring, results for increased risk for breast cancer and endometrial cancer following exposure to ovarian stimulation medications are inconclusive. Larger population studies with longer periods of follow-up and better adjustment for confounding factors are needed.

Objective: To report all pregnancies to date after magnetic resonance-guided focused ultrasound surgery (MRgFUS) for the conservative treatment of clinically significant uterine fibroids., Design: Prospective registry of all known pregnancies occurring after MRgFUS maintained by the device manufacturer and reported to the Food and Drug Administration., Setting: World experience of pregnancies after treatment with reports from 13 sites in seven countries., Patient(s): Fifty-one reproductive-age women with uterine leiomyomas., Intervention(s): Women underwent MRgFUS treatment for symptomatic uterine leiomyomas before this report., Main Outcome Measure(s): Pregnancy outcomes and complications., Result(s): Fifty-four pregnancies in 51 women have occurred after MRgFUS treatment of uterine leiomyomas. The mean time to conception was 8 months after treatment. Live births occurred in 41% of pregnancies, with a 28% spontaneous abortion rate, an 11% rate of elective pregnancy termination, and 11 (20%) ongoing pregnancies beyond 20 gestational weeks. The mean birth weight was 3.3 kg, and the vaginal delivery rate was 64%., Conclusion(s): Preliminary pregnancy experience after MRgFUS is encouraging, with a high rate of delivered and ongoing pregnancies., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The quality of proxy reports provided by husbands regarding women's health, when the index case (the wife) cannot be interviewed, is controversial., Study Design: Fourteen husbands and wives at menopause were interviewed separately using the same pre-constructed questionnaire. The extent of agreement between their reports was assessed., Results: Higher agreement was noted for questions regarding physiognomy, number of live children, age at menopause and general health problems. Lesser agreement was observed regarding obstetric history., Conclusions: In light of these preliminary observations, the use of husbands as proxy for women's health questionnaire at midlife should be carefully considered and may be limited to questions regarding general health issues rather than reproductive health.

Introduction: Focused ultrasound under real-time MR guidance and control (MRgFUS) can be used for the thermal ablation of tissue. Currently this technique is used clinically for the noninvasive treatment of uterine leiomyomas and is in clinical evaluation for breast cancer, adenomyosis and other indications. MRgFUS is being tested for pain relief in patients suffering from bone metastases. This is the first case to report on MRgFUS for pain relief in patients suffering from recurrent cervical carcinoma., Case Report: A 29-year-old patient with recurrent squamous cell carcinoma of cervix following radical hysterectomy, chemotherapy and radiation was treated by MRgFUS due to pelvic mass unresponsive to conventional treatment that caused intractable pain. Following two treatments the patient experienced a marked reduction in pain and increase in Karnovsky Performance Status (KPS) from 50% to 80%., Discussion: Palliative treatment of pain with noninvasive MRgFUS in cases of recurrent cervical carcinoma may be a safe and efficient alternative to other invasive techniques.

Objective: Hysterectomy or myomectomy are the accepted treatments for symptomatic uterine fibroids. Heat ablation of uterine fibroids has been shown to be an effective alternative treatment. The aim of this study was to determine the clinical efficacy of non-invasive thermal ablation by transcutaneous magnetic resonance-guided high-intensity focused ultrasound (MRgFUS) for the treatment of symptomatic uterine fibroids., Methods: In this prospective study, MRgFUS ablation of uterine fibroids was performed in 35 symptomatic women scheduled for hysterectomy. Clinical symptoms, patient satisfaction and uterine size were determined at 1 month and 6 months after the procedure., Results: This outpatient procedure was very well tolerated by all women. Sixty-nine percent (24/35) of the treated patients reported either significant or partial improvement in symptoms. Treated fibroids decreased in volume by 12% and 15% at 1 and 6 months, respectively. Minor transient side-effects were observed in two women. Six women underwent hysterectomy during the follow-up period., Conclusion: This study demonstrates the clinical efficacy of MRgFUS ablation of uterine fibroids. This novel, non-invasive surgical approach may offer an alternative therapy for women with uterine fibroids., (Copyright (c) 2007 ISUOG)

Objective: To assess several measures of the long-term outcome of magnetic resonance-guided focused ultrasound surgery for symptomatic uterine leiomyomata., Methods: Data on 359 women completing 24-month follow-up in all clinical trials of magnetic resonance-guided focused ultrasound surgery for uterine leiomyomata were analyzed. Quality of life outcomes, measured by the symptom severity score of the Uterine Fibroid Symptoms Quality Of Life Questionnaire were assessed for 24 months after treatment. Clinical endpoints, including uterine shrinkage, the need for additional leiomyoma treatment, and the time to additional leiomyoma treatment, were all assessed. The nonperfused volume ratio after treatment, calculated from the gadolinium-enhanced magnetic resonance imaging after treatment and the best measure of tissue necrosis after treatment, was used to assess outcome based on completeness of leiomyoma ablation., Results: Women undergoing magnetic resonance-guided focused ultrasound surgery for symptomatic uterine leiomyomata have durable symptom relief, as measured by the symptom severity score at 24 months, with significantly greater improvement with more complete ablation (P<.001). Survival analysis demonstrates a significant reduction in the percentage of women undergoing additional leiomyoma treatment (P=.001) in women in the high nonperfused volume group. The mean shrinkage and mean residual nonperfused volume ratio are both significantly above zero at 6 months in the high nonperfused volume group (P<.001). The incidence of adverse events is low. However, for women with minimal treatment, the risk of additional procedures is high., Conclusion: Magnetic resonance-guided focused ultrasound surgery is an effective treatment for uterine leiomyomata and results in sustained symptomatic relief., Level of Evidence: III.

Context: Ovulation induction drugs may be associated with increased breast cancer risk. Results so far have been inconclusive., Objective: To evaluate the association between infertility, exposure to ovulation induction drugs and the incidence of breast cancer., Design: Historical prospective cohort and nested case-control study., Setting: Institutional practice, Patients: About 5,788 women attending five infertility centers in Israel between 1964 and 1984., Intention: Abstracting of medical records and telephone interviews., Main Outcome Measure: Breast cancer incidence was determined through linkage with the National Cancer Registry database. Standardized incidence ratios (SIRs) and 95% confidence intervals were computed by comparing the observed to the expected cancer rates in the general population. In addition, a nested case-control study within the cohort was performed with interviews of breast cancer cases and two matched controls., Results: The study cohort included 120,895 women years of follow-up. Compared to 115.2 expected breast cancer cases, 131 cases were observed (SIR = 1.1; 95% CI 0.9-1.4). Risk for breast cancer was significantly higher for women treated with clomiphene citrate (SIR = 1.4; 95% CI 1.0-1.8). Similar results were noted when comparisons were carried out between treated and untreated women, and when multivariate models were applied. In the nested case-control study, higher cycle index (OR = 2.2; 95% CI 1.0-4.8) and treatment with clomiphene citrate (OR=2.7; 95% CI 1.3-5.7) were associated with higher risk for breast cancer., Conclusion: Infertility and usage of infertility drugs in general are not associated with increased risk for breast cancer. However, for infertile women treated with clomiphene citrate, breast cancer risk is elevated.

Background: Menorrhagia is a serious complication in young female oncology patients who suffer from severe thrombocytopenia during myelosuppressive treatment. To the authors' knowledge, little is known regarding the incidence of this complication or the effectiveness of possible therapies for its prevention., Methods: In this retrospective clinical study, after a thorough gynecologic evaluation, young female oncology patients with regular menstrual cycles undergoing myelosuppressive treatments received either depo-medroxyprogesterone acetate (DMPA), or D-tryptophan-6-luteinizing hormone-releasing hormone depot treatment (gonadotropin-releasing hormone agonist [GnRH-a]), or no treatment before the administration of myelosuppresive chemotherapy. Only patients who later developed severe thrombocytopenia (<25,000 platelets per muL) were included in the study. Daily blood counts, menorrhagia, nonvaginal bleeding episodes, and the need for blood products, gynecologic consultations, and other medical interventions were determined., Results: Of 101 women with cancer who met the inclusion criteria, 42 patients received DMPA, 39 patients received GnRH-a, and 20 patients remained untreated. The mean duration (+/- standard deviation) of severe thrombocytopenia was 24.76 +/- 23.6 days. Four patients were not included because of significant gynecologic pathologies. General bleeding from nongynecologic sites was similar for all groups and was not associated with vaginal bleeding. Severe or moderate menorrhagia was documented in none of the 39 women who received GnRH-a, in 9 patients (21.4%) who received DMPA, and in 9 untreated patients (40%; P = .02). Fewer calls for urgent gynecologic consultations were documented in the GnRH-a group compared with the untreated group (P < .0001)., Conclusions: Female patients undergoing myelosupressive therapy are at high risk of developing significant menorrhagia during prolonged, severe thrombocytopenia. Pretreatment gynecologic evaluation can detect significant pelvic pathologies. GnRH-a treatment effectively prevented menorrhagia, whereas DMPA administration was less effective., ((c) 2006 American Cancer Society.)

The Purpose of This Study: To evaluate the safety and efficacy of an enhanced magnetic resonance-guided focused ultrasound (MRgFUS) emission protocol that results in more extensive treatment by increasing the volume of each focal ablation using the same energy., Materials and Methods: Six pigs were treated with an MRgFUS system combined with real-time MR, for imaging and temperature mapping, with 102 "enhanced" and 97 "regular" focal ablations performed on both buttock muscles. Real-time imaging, temperature mapping, and acoustic reflected spectrum data enabled immediate evaluation of the results. MR contrast-enhanced images and pathology examinations were used for confirmation., Results: The location of the ablated volume by "enhanced" sonication is predictable, with a maximum possible shift of 6 mm toward, and 3 mm away, from the transducer. The ablated volume after enhanced sonication was, on average, 1.8 times larger than after a regular sonication of the same energy. Pathology results showed the same thermally induced damage patterns in the enhanced sonications and the regular sonications., Conclusion: Accelerated MRgFUS with enhanced sonication is a safe, controllable, and more effective tissue ablative modality than standard sonication. This new technology may significantly reduce the length of tumor ablation procedures. (Isn't the new technology you're talking about MRgFUS? If so, you don't need to repeat it at the end of this sentence.).

This chapter demonstrates that new interventional techniques have been introduced over recent years in order to find an adequate non-invasive therapy for adenomyosis. There is no evidence-based medicine to guide us in the treatment of adenomyosis with minimally invasive therapy. In fact, most data regarding adenomyosis and these evolving therapies comes from the inadvertent treatment of adenomyosis in studies designed to treat uterine leiomyomas. Essentially, all data are from case reports or small case series. The problem is compounded by the fact that there is no agreed imaging definition of adenomyosis, and so therapies that do not excise the uterus have no 'gold standard' for comparison. Nonetheless, there are some reports suggesting that there may be efficacy in techniques such as medicated intrauterine devices, uterine artery embolization, and MRI-guided focused ultrasound surgery. Larger studies specifically treating adenomyosis are clearly required. As with every new approach, the widespread success of these techniques will depend on the general adoption of adequate diagnostic solutions and improvements in the technical parameters of these new regimens. Since the techniques presented in this chapter are new, they have not yet undergone the necessary thorough scientific scrutiny and discussion that is needed for their general acceptance. In the past, adenomyosis was mainly a 'post-factum' pathological diagnosis after extensive surgery. Based on the evidence presented in this chapter it seems that adenomyosis has become an entity that might be treatable by new, minimally invasive or non-invasive treatments.

Adequate ovarian response, essential for successful IVF, cannot be accurately predicted. This study retrospectively reviewed all patients undergoing IVF from 1998 to 2001. Inclusion criteria were age <41 years at treatment onset and a basal day 3 serum FSH concentration <12 IU/l. Women with FSH or=3 in group 1 and <3 in group 2 (controls). Age at treatment initiation, basal serum day 3 FSH and LH concentrations, peak serum oestradiol concentration, number of retrieved and fertilized oocytes and pregnancy rate were analysed. Groups 1 (n = 41, 111 IVF treatment cycles) and 2 (n = 596, 1,434 IVF treatment cycles) were similar in term of woman's mean age. Group 1 had significantly higher mean basal day 3 FSH concentration (P < 0.01) and significantly lower oestradiol concentrations at oocyte retrieval (P < 0.01), mean number of oocytes retrieved and fertilized (P < 0.01) and pregnancy rate (P = 0.016). The same trend persisted after excluding 98 patients with basal FSH concentrations >8 IU/l. In conclusion, elevated day 3 FSH/LH ratio is associated with an inferior outcome in IVF treatment cycles and may be used as an additional predictor for decreased ovarian response.

Objective: To assess outcomes at 6 and 12 months after magnetic resonance-guided focused ultrasound surgery (MRgFUS) for symptomatic uterine leiomyomas., Design: Multicenter clinical trial., Setting: Academic medical centers., Patient(s): Premenopausal women with symptomatic uterine leiomyomas and no plans for future pregnancy (n = 109 at 6 months and n = 82 at 12 months)., Intervention(s): A single treatment session of MRgFUS for uterine fibroids., Main Outcome Measure(s): Reduction in fibroid symptoms as measured by the symptom severity score (SSS) of the Uterine Fibroid Quality-of-Life Instrument (UFS-QOL), the only validated measure of leiomyoma symptomatology. A 10-point reduction in the SSS was selected as the targeted improvement., Result(s): Seventy-one percent of women undergoing MRgFUS reached the targeted symptom reduction at 6 months, and 51% reached this at 12 months. The magnitude of improvement in SSS was greater than predicted, with subjects having a mean decrease of 39% and 36% at 6 and 12 months, respectively. This paralleled the improvement seen using the short form-36 instrument. A modest volume reduction similar in magnitude to the treated volume was seen. The incidence of adverse events was low., Conclusion(s): MRgFUS treatment results in short-term symptom reduction for women with symptomatic uterine leiomyomas with an excellent safety profile.

Objective: The purpose of this study was to explore our hypothesis that MRI-guided focused ultrasound therapy for the treatment of uterine fibroids will lead to a significant reduction in symptoms and improvement in quality of life. We describe focused ultrasound therapy applications and the method for monitoring the thermal energy deposited in the fibroids, including the MRI parameters required, in a prospective review of 108 treatments., Materials and Methods: Patients presenting with symptomatic uterine fibroids who attained a minimal symptom severity score and who would otherwise have been offered a hysterectomy were recruited. Thermal lesions were created within target fibroids using an MRI-guided focused ultrasound therapy system. The developing lesion was monitored using real-time MR thermometry, which was used to assess treatment outcome in real time to change treatment parameters and achieve the desired outcome. Fibroid volume, fibroid symptoms, and quality-of-life scores were measured before treatment and 6 months after treatment. Adverse events were actively monitored and recorded., Results: In this study, 79.3% of women who had been treated reported a significant improvement in their uterine fibroid symptoms on follow-up health-related quality-of-life questionnaires, which supports our hypothesis. The mean reduction in fibroid volume at 6 months was 13.5%, but nonenhancing volume (mean, 51 cm(3)) remained within the treated fibroid at 6 months., Conclusion: This early description of MRI-guided focused ultrasound therapy treatment of fibroids includes follow-up data and shows that, although the volume reduction is moderate, it correlates with treatment volume and the symptomatic response to this treatment is encouraging.

Background: It has remained controversial whether and in what way suppression of the pituitary-gonadal axis using GnRH analogues can reduce the destructive effects of chemotherapy on ovarian primordial follicles and thus prevent ovarian failure. GnRH antagonists suppress gonadotrophin levels immediately after administration. In this study we determined whether administration of the GnRH antagonist cetrorelix before exposure to increasing doses of cyclophosphamide (Cy) affected the number of surviving primordial follicles (PMF) in the mice ovary., Methods: Highly inbred young Balb/c mice (114 females) were injected with 0, 50 and 75 mg/kg of Cy. In each treatment group, half of the females were injected daily with cetrorelix starting 9 days before and 7 days post-administration of Cy. In serial sequential ovarian sections the total number of PMF in both ovaries was counted., Results: Ovaries exposed to Cy at doses of 50 and 75 mg/kg had significantly fewer PMF than those in the control group (P < 0.01). In each of the Cy groups used, pretreatment with cetrorelix resulted in significantly higher numbers of PMF: in the 50 mg/kg Cy group only 14% were destroyed (cetrorelix group) versus 53% (P < 0.001), while in the 75 mg/kg Cy group only 35% of PMF were destroyed versus 54% in animals treated only with Cy (P < 0.004). The interaction between the effect of cetrorelix and the different doses of Cy did not reach statistical significance (P = 0.089, two-way ANOVA)., Conclusions: Administration of the GnRH antagonist cetrorelix to mice significantly decreases the extent of ovarian damage induced by the chemotherapeutic agent Cy. The use of different substerilizing doses of Cy suggested that the extent of protection achieved by the antagonist is dose-dependent and decreases with increasing Cy doses. The results of this study may suggest a possible similar beneficial effect in women undergoing chemotherapy, can explain the discrepancy in results of existing clinical studies and indicate possible pathways for ovarian GnRH agonist protection. Further research and clinical studies are needed in order to confirm these results.

Objective: The purpose of this study was to determine the safety and efficacy of focused ultrasound surgery with magnetic resonance imaging guidance for the noninvasive treatment of uterine leiomyomas., Study Design: Fifty-five women with clinically significant uterine leiomyomas were treated. Pain and complications were assessed prospectively, and posttreatment magnetic resonance imaging was used to measure the treatment effects. Patients in three of the five centers underwent planned hysterectomy after treatment, which provided pathologic correlation of treatment., Results: Seventy-six percent of the enrolled patients completed the full treatment session. All treatments were conducted in an outpatient setting with minimal discomfort for subjects and no major complications. Pathologic examination of the uterus confirmed that magnetic resonance imaging guidance provides the safe and accurate delivery of effective levels of thermal energy with a 3-fold increase in volume of histologically documented necrosis, compared with treatment volume (6.6 +/- 0.8 vs 18.4 +/- 3.9 mL, P <.005)., Conclusion: Magnetic resonance imaging-guided focused ultrasound surgery appears to be a well-tolerated treatment for uterine leiomyomas.

Objective: We sought to determine whether raloxifene effects the ovarian circulation in women after menopause., Study Design: The resistance indices of the ovarian blood flow were assessed in 130 women after menopause who were randomly assigned to receive either 60 mg of raloxifene, a continuous combined estrogen-progestin tablet daily, or neither treatment for 24 months., Results: The women who received raloxifene or hormonal replacement therapy had a significant time-related decrease in the resistance index of the ovarian artery blood flow compared to baseline values (resistance index, 0.91) starting after 12 and 18 months of treatment (resistance index, 0.88 and 0.89, respectively; P <.002 and.001, respectively). Whereas significant increases in the resistance index respective to the prestudy values were observed in the nontreated women at 24 months (resistance index, 0.93; P <.0001). The mean (+/-SD) resistance index of the ovarian blood flow at the end of the study (resistance index, 0.89) was significantly lower in the women who were treated with raloxifene than in the women who were treated with hormone replacement therapy (P <.002). No changes in the ovarian dimensions or appearance were noticed during the entire study., Conclusion: Daily therapy with raloxifene has significant ovarian vascular-relaxing effect in women after menopause. This potentially important direct vasculoprotective long-term effect of raloxifene on cardiovascular disease deserves further investigation.

Objective: To determine the prevalence of markers of thrombophilia in women hospitalized for severe OHSS., Design: Prospective study., Setting: Academic research center., Patient(s): Women undergoing induction of ovulation complicated by severe OHSS (n = 20) and women undergoing induction of ovulation without development of severe OHSS (n = 41)., Intervention(s): Blood samples to test for markers of thrombophilia were obtained during the luteal phase of the treatment cycle., Main Outcome Measure(s): Blood samples were analyzed for markers of thrombophilia, such as plasma levels of antithrombin, protein S and protein C, antiphospholipid antibodies, the factor V Leiden mutation, and 677T polymorphism in the 5,10 methyltetrahydrofolate reductase (MTHFR 677T) gene., Result(s): Seventeen of 20 patients with severe OHSS (85%) and 11 of 41 controls (26.8%) had one or more positive markers of thrombophilia. Of the women with severe OHSS, 6 had a decreased antithrombin level, 8 had decreased levels of protein S, 7 were homozygous for the MTHFR 677T mutation, 1 was heterozygous for the factor V Leiden mutation, and 5 had antiphospholipid antibodies. Eight women with OHSS and no controls had more than one positive marker of thrombophilia., Conclusion(s): The prevalence of thrombophilia is increased in women with severe OHSS. These findings suggest that prophylactic screening for this disorder and possible use of heparin prophylaxis for thromboembolic phenomena should be considered in these patients.

Objective: To assess whether ovarian hyperstimulation and IVF increase the risk for cancer., Design: Historical cohort analysis. SETTING; IVF units of two medical centers in Israel., Patient(s): Five thousand twenty-six women who underwent IVF between 1981 and 1992. INTERVENTION(S); Cancer incidence rates were determined through linkage to the National Cancer Registry and were compared with expected rates with respect to age, sex, and place of birth., Main Outcome Measure(s): Development of cancer., Result(s): Twenty-seven cases of cancer were observed, and 35.6 were expected (standardized incidence ratio, 0.76 [95% CI, 0.50-1.10]). Eleven cases of breast cancer were observed, whereas 15.86 were expected (standardized incidence ratio, 0.69 [95% CI, 0.46-1.66]). One case of ovarian cancer and 1 case of cervical cancer were observed, compared with 1.74 and 1.73 cases expected, respectively. The type of infertility, number of IVF cycles, and treatment outcome did not significantly affect risk for cancer., Conclusion(s): In a cohort of women treated with IVF, no excess risk for cancer was noted.

Background: This is the first report of human exposure to the novel compound follicle stimulating hormone (FSH)-C-terminal peptide (CTP) 'FSH-CTP' (Org 36286), a long-acting recombinant FSH like substance, consisting of the alpha-subunit of human FSH and a hybrid beta-subunit. The latter is composed of the beta-subunit of human FSH and the C-terminus part (CTP) of the beta-subunit of human chorionic gonadotrophin (HCG)., Methods: In this phase I, non-blind, multi-centre study, 13 hypogonadotrophic hypogonadal male subjects were enrolled to test the safety of FSH-CTP in terms of antibody formation in humans. Furthermore, the pharmacokinetic profile of this new compound was determined. Subjects were injected four times with 15 microg FSH-CTP with an interval of approximately 4 weeks between each injection., Results: No drug related (serious) adverse events occurred. No antibodies against FSH-CTP or chinese hamster ovary (CHO)-cell derived proteins were detected and measurement of local tolerance demonstrated that s.c. administration of FSH-CTP is well tolerated and no increase in intensity of injection-site responses was observed after repeated exposure to FSH-CTP. After the first and third injection, FSH-CTP serum concentrations were determined. Overall mean (+/- SD) C(max) was 0.426 (+/- 0.116) ng/ml, mean t(1/2) and AUC(0-infinity) were 94.7 (+/- 26.2) h and 81.5 (+/- 18.8) ng.h/ml respectively. Compared with recFSH (Puregon), the half life of FSH-CTP was increased 2-3 times. Following the first and third injection a clear rise in serum inhibin-B concentrations were observed., Conclusions: The use of FSH-CTP is safe and does not lead to detectable formation of antibodies. Furthermore, the pharmacokinetic and dynamic profile of FSH-CTP may lead to the development of new, more convenient regimens for the treatment of male and female infertility.

Objective: To determine the preferred treatment modality in patients with PCOS who experienced premature luteinization during CC treatment., Design: Prospective randomized study., Setting: Tertiary medical center., Patients: Twenty-two infertile women with PCOS demonstrating premature luteinization during at least two consecutive CC cycles., Interventions: Randomized induction of ovulation either with FSH alone or with GnRH agonist combined with FSH for a single treatment cycle., Main Outcome Measures: Premature luteinization was defined as serum progesterone >1.5 ng/mL before hCG administration., Results: Premature luteinization occurred in eight of the 10 patients (80%) in group A and in two of the 12 patients in group B (16.6%). This result corresponds to the higher mean (+/-SD) progesterone level present in group A patients as compared to those in group B (2.0 +/- 1.2 ng/mL vs. 1.2 +/- 0.6 ng/mL, P=0.03). No pregnancies were achieved in group A, whereas the pregnancy rate per cycle observed in group B was 33.3% (4/12). On the day of hCG administration, the maximum mean (+/-SD) estradiol level was significantly lower (P<0.0001) in group A (210.6 +/- 37.9 pg/mL) than in group B (600.3 +/- 253.8 pg/mL). The treatment duration and the number of FSH ampules used did not differ between the groups., Conclusions: Pituitary desensitization with GnRH analog in combination with FSH is superior to FSH-only treatment in PCOS patients who demonstrate premature luteinization during CC treatment.