Assessment of the climacteric syndrome: a narrative review.

PURPOSE: Many menopausal women suffer from a variety of estrogen deficiency-related symptoms and chronic medical conditions. Health care professionals should be able to identify and quantify symptoms to facilitate diagnosis, indicate and monitor treatment. Therefore, various questionnaires have been developed and are used as a simple, time-saving and cost-effective mean to assess and monitor menopausal complaints. The aim of this review is to provide an overview and comparison of the available tools for climacteric syndrome assessment. METHODS: Three electronic databases (Pubmed, EMBASE and Cochrane Database of Systematic Reviews/CDRS) were searched covering a time period of 10 years using a combination of relevant controlled vocabulary terms and free-text terms. Relevant references were evaluated for inclusion in a stepwise approach. RESULTS: The literature research revealed four questionnaires (Kupperman Index, Menopause Rating Scale, Menopause Specific Quality of Life Questionnaire and Greene Climacteric Scale) that are used to holistically assess the climacteric syndrome, varying in type of assessment, included symptoms, rating system of severity, weighing of symptoms, resulting total rating score and validation status. Further questionnaires are available to assess single symptoms or group of symptoms relating to specific aspects of menopause (e.g., vasomotor symptoms, insomnia, etc.). CONCLUSION: Four holistic questionnaires addressing menopausal symptoms have been developed [KI, MRS, MENQOL (-Intervention), Greene Climacteric Scale]. All but one (KI) have been validated and are available in different languages. However, there are still several shortcomings such as the lack of recognition of ethnic and cultural background and missing thresholds for treatment initiation and monitoring.

Vitrification of human pronuclear oocytes by direct plunging into cooling agent: Non sterile liquid nitrogen vs. sterile liquid air.

In fact, a full sterilization of commercially-produced liquid nitrogen contaminated with different pathogens is not possible. The aim of this study was to compare the viability of human pronuclear oocytes subjected to cooling by direct submerging of open carrier in liquid nitrogen versus submerging in clean liquid air (aseptic system). One- and three-pronuclei stage embryos (n = 444) were cryopreserved by direct plunging into liquid nitrogen (vitrified) in ethylene glycol (15%), dimethylsulphoxide (15%) and 0.2M sucrose. Oocytes were exposed in 20, 33, 50 and 100% vitrification solution for 2, 1 and 1 min, and 30-50 s, respectively at room temperature. Then first part of oocytes (n = 225) were directly plunged into liquid nitrogen, and second part of oocytes (n = 219) into liquid air. Oocytes were thawed rapidly at a speed of 20,000 °C/min and then subsequently were placed into a graded series of sucrose solutions (0.5, 0.25, 0.12 and 0.06M) at 2.5 min intervals and cultured in vitro for 3 days. In both groups, the rate of high-quality embryos (Grade 6A: 6 blastomeres, no fragmentation; Grade 8A: 8 blastomeres, no fragmentation; Grade 8A compacting: 8 blastomeres, beginning of compacting) was noted. The rates of high-quality embryos developed from one-pronuclear oocytes vitrified by cooling in liquid nitrogen and liquid air were: 39.4% ± 0.6 and 38.7% ± 0.8, respectively (P > 0.1). These rates for three-pronuclear oocytes were: 45.8 ± 0.8% and 52.0 ± 0.7%, respectively (P < 0.05). In conclusion, vitrification by direct submerging of oocytes in clean liquid air (aseptic system) is a good alternative for using of not sterile liquid nitrogen.

Symptoms of uterine myomas: data of an epidemiological study in Germany.

PURPOSE: Currently, no reliable data are available concerning the type and frequency of symptoms in premenopausal women with uterine myomas. METHODS: 2296 women were examined by means of vaginal ultrasound for the presence of myomas in seven gynaecological outpatient departments in Germany. From this population, 1314 premenopausal women between the ages of 30 and 55 years were evaluated to determine the type and frequency of myoma-related symptoms and their relationship to anamnestic factors, and the number, size, and location of the myomas. Standardised questionnaires were used to record the symptoms. RESULTS: Prevalence: In almost every second premenopausal woman (n = 639; 48.6%), uterine myomas were diagnosed. The frequency of myomas increased continuously with age and was highest in women between 46 and 50 years (65.2%). Age itself was found to be the main risk factor for the presence of myomas (p < 0.001). SYMPTOMS: 54.3% (n = 347) of the women suffered from myoma-related symptoms. The four main symptoms were identified as: Heavy menstrual bleeding (40.7%), dysmenorrhoea (28.2%), lower abdominal pain (14.9%), and intermenstrual bleeding (14.1%). In the majority of cases, the symptoms occurred simultaneously. Determinants for symptoms: Symptoms did not follow a clear age-related trend, whilst the number and size of the myomas did determine the presence of symptoms. The main influencing factor for the presence of intermenstrual bleeding was the location of the myomas. CONCLUSIONS: The high prevalence of uterine myomas highlights the importance of the diagnosis uterine myomas in standard gynaecological practice: The presence of only one myoma caused symptoms in 46.5% and small myomas of up to 2 cm in diameter resulted in symptoms in 39.5%.

Prevalence of uterine myomas in women in Germany: data of an epidemiological study.

PURPOSE: Currently, no reliable data are available concerning the prevalence of uterine myomas in Germany. In this prospective study, we examined the prevalence of myomas in women older than 30 years by means of vaginal ultrasound. METHODS: 2296 women, who consented to the procedure, were examined by means of vaginal ultrasound for the presence of myomas in seven gynaecological outpatient departments in Germany. PREVALENCE: myomas were detected in 41.6 % of all women. Age dependence: With increasing age, the prevalence of uterine myomas rose from 21.3 % (30-35 years) to 62.8 % (46-50 years). Later, the number of myomas decreased again from 56.1 % (51-55 years) to 29.4 % in women older than 55 years. Menarche/BMI: no correlation could be found between the age at first menstrual period or the body mass index and the occurrence of myomas. Parity: since the group of nulliparous women and the group of women with more than four deliveries stand out by increased occurrence of myomas, a non-linear correlation seems to exist, necessitating more in-depth discussion with regard to age dependency. CONCLUSIONS: The results of this study suggest that more than 40 % of women over 30 years of age suffered from myomas and more than 50 % of all women in Germany may develop uterine myomas at some time in their life.

Transplantation of cryopreserved human ovarian tissue: restoration of reproductive function after two cycles of radio- and chemo-therapeutic treatments.

BACKGROUND: Patient S. was born in 1983, developed a Ewing-Sarcoma and obtained low dose chemotherapy in 1996. In 2007, Patient S. received high-dose chemotherapy because lung-metastases were diagnosed. The aim of the study was to investigate the health of cryopreserved ovarian tissue and also to examine whether this ovarian tissue can restore the reproductive function of patient after two cycles of radio-and chemo-therapeutic treatments. METHODS: Twenty pieces of ovarian tissue (total of approximately 200 mm2) were conventionally frozen with 6% (v/v) dimethyl sulfoxide, 6% (v/v) ethylene glycol and 0.15 M sucrose and kept for five years before 8 pieces were thawed and transplanted back into the patient. Two small (1 x 2 x 1 mm) pieces of this thawed tissue were cultured in a chicken embryonic chorioallantoic membrane (CAM)-system for 5 days to assess the tissue viability. RESULTS: The ovarian tissue that was grafted re-established spontaneous menstrual bleeding within five months and serum 17-beta estradiol increased from 19 to 330 pg/mL. Ultrasound revealed a dominant follicle at the site of the transplanted tissue in the follicular phase after the menstrual bleed. Analysis of the CAM cultured tissue established that 88% of the primordial follicles had degenerated and there was limited growth of blood vessels. CONCLUSIONS: In spite of the damage caused by the cryopreservation the surviving follicles could restore ovarian function after re-transplantation.

Viability of human ovarian tissue confirmed 5 years after freezing with spontaneous ice-formation by autografting and chorio-allantoic membrane culture.

To achieve optimal and uniform outcomes, slow cooling protocols for human ovarian tissues generally initiate ice formation at high sub-zero temperatures (-6 to -9 °C). The aim of the study was to investigate the function of ovarian tissue that had unintentionally self seeded at -20 °C during the freezing step, by examining its development following chicken embryonic chorioallantoic membrane (CAM) grafting and after transplantation back to the patient. Ovarian tissue was frozen in 6% (v/v) dimethyl sulfoxide, 6% (v/v) ethylene glycol and 0.15M sucrose which had self-seeded at -20 °C. Five years after cryopreservation, 8 pieces were thawed and transplanted back to the patient. Two small (1 × 2 × 1 mm) pieces of this thawed tissue were cultured in a CAM-system for 5 days to assess the tissue viability. The autografted ovarian tissue re-established spontaneous menstrual bleeding within five months and raised serum 17-ß Estradiol from 19 to 330 pg/ml. Ultrasound revealed a dominant follicle at the site of the transplanted tissue in the follicular phase after the menstrual bleed. Analysis of the CAM cultured tissue established that 88% of the primordial follicles are degenerated and there was limited in growth of blood vessels. In conclusion, in spite of the damage caused by the cryopreservation with spontaneous ice-formation the viability could be confirmed by CAM culture and the restoration of ovarian function after auto-transplantation.

Risk-reducing salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers.

BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) is often recommended to carriers of deleterious breast cancer gene 1/2 (BRCA1/2) mutations in order to reduce their breast cancer risk by 50% and their ovarian cancer risk by approximately 95%. To evaluate the acceptance, timing, histopathology findings and follow-up results we retrospectively analyzed a cohort of BRCA1/2 mutation carriers who underwent risk-reducing salpingo-oophorectomies. METHODS: Between 1996 and 2009, 306 women who tested positive for a BRCA1 or BRCA2 mutation were counseled for preventive options. RRSO was recommended to all mutation carriers at age 40 or 5 years prior to the earliest occurrence of ovarian cancer in the family. Data from 175 BRCA mutation carriers (92 BRCA1 and 83 BRCA2), who decided to undergo a RRSO, were analyzed. Data were collected from study entry until recent follow-up. RESULTS: Fifty-seven percent of BRCA mutation carriers opted for RRSO. Mean age at time of surgery was 47 years. Overall, one occult carcinoma of the fallopian tube was detected at the time of surgery in a 57-year-old woman and one primary peritoneal carcinoma occurred 26 months after RRSO in a 59-year-old woman. CONCLUSION: Risk-reducing salpingo-oophorectomy is widely accepted. Recommendation of surgery at the age of 40 seems to be safe and the frequency of extraovarian primary peritoneal carcinoma after surgery is low.

Is there an association between septate uterus and endometriosis?

BACKGROUND: The question of whether Müllerian anomalies are significantly more often combined with endometriosis is a controversially discussed problem. Some publications described this association in patients with obstructive but not non-obstructive Müllerian anomalies or controls without Müllerian anomalies. The aim of this study was to evaluate the incidence of endometriosis in patients with a septate uterus as a non-obstructive form of Müllerian anomalies. METHODS: In a retrospective study, we evaluated 120 patients (29.4 +/- 4.7 years; mean +/- SD) with a septate uterus. The control group consisted of 486 consecutive infertile patients (30.8 +/- 6.3 years) with a normal hysteroscopy and laparoscopy. RESULTS: The incidence of dysmenorrhoea was comparable in both groups, but the incidence of endometriosis was significantly higher in patients with a septate uterus (25.8 versus 15.2%, P = 0.006). CONCLUSION: Our results suggest a higher incidence of endometriosis in patients with a septate uterus. If it can be confirmed by others, the initial finding of a septate uterus in infertile patients should be followed by a combined hysteroscopy and laparoscopy.

Monozygotic triplets and monozygotic twins after ICSI and transfer of two blastocysts: case report.

There are data regarding the possible influences of extended embryo culture to the blastocyst stage as well as zona pellucida manipulation on the incidence of monozygotic multiples. This is interesting, as one aim of extended culture with embryo selection is to minimize the multiple pregnancy rate. We report, to our knowledge, on the first case of monozygotic twins and monozygotic triplets after ICSI and the transfer of two blastocysts. Monozygotic multiples after ICSI and blastocyst transfer and the resulting problems are another reason to encourage the transfer of only one blastocyst. Theories about risk factors and the pathophysiology of monozygotic multiples will be discussed both in terms of this case report and of the literature. In our opinion, the incidence of 5.9-8.9% monozygotic multiple occurrence after ICSI and blastocyst transfer reported in the literature requires that patients are informed of the uncertainties until this phenomenon and its risk factors are better understood.

Minihysteroscopy as routine diagnostic procedure in women with primary infertility.

STUDY OBJECTIVE: To evaluate the importance of routine minihysteroscopy in the diagnosis of primary infertility. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: Endoscopic center at a university hospital. PATIENTS: Three hundred seventy-nine patients with primary infertility. INTERVENTION: Diagnostic minihysteroscopy without anesthesia or sedation. MEASUREMENTS AND MAIN RESULTS: Hysteroscopy was normal in 337 patients (89.9%). In 38 patients (10.1%) an intrauterine pathology was found: 26 intrauterine adhesions, 12 cases of uterus subseptus. The procedure could not be completed in four women. CONCLUSION: Minihysteroscopy should become a routine diagnostic procedure in women with primary infertility, even those with no suspected intrauterine pathology or other risk factors.

Effect of soy supplementation on endogenous hormones in postmenopausal women.

AIM: The purpose of this study was to investigate the effect of soy supplementation with isoflavones on plasma hormone levels in postmenopausal women. METHODS: 16 postmenopausal women (mean age 56.21 +/- 5.01 years) were assigned to 24 weeks of dietary soy supplementation. A defined soy protein amount per day (20 g) with a low dosage of isoflavones (20 mg) was used. Plasma samples were analyzed for estradiol, FSH, LH, prolactin, testosterone and DHEAS. RESULTS: After 24 weeks of soy supplementation, plasma levels of estradiol did not increase. Gonadotropins, prolactin and the measured plasma androgens remained unchanged. We did not see any significant treatment effects. CONCLUSIONS: In the postmenopausal hypoestrogenic situation, soy protein consumption with low isoflavones does not influence endogenous hormone levels of estradiol and gonadotropins.

Glycodelin serum levels in women with ectopic pregnancy.

OBJECTIVE: Aim of our study was to determine circulating levels of glycodelin for biochemical monitoring of women with vaginal bleeding and/or abdominal pain in early pregnancy. The objective was, using glycodelin as a biochemical parameter, to distinguish between incomplete abortion and ectopic pregnancy in early weeks of gestation. STUDY DESIGN: In 169 women with a first trimester pregnancy, a single serum measurement of maternal glycodelin was taken. Patients were divided into groups according to the clinical and/or ultrasonografic findings at the time of hospitalisation:ectopic pregnancy, incomplete abortion and control. RESULTS: Glycodelin serum levels were significantly lower in patients with ectopic pregnancy comparable with intact pregnancy and incomplete abortion. There was no difference in serum levels between intact pregnancy and incomplete abortion. CONCLUSION: Glycodelin might represent a biochemical parameter in the differential diagnosis between ectopic pregnancies and incomplete abortion. The number of patients was too small to give reference ranges for pregnancy weeks.

Implantation despite an extensive endometrial defect after hysteroscopic resection of symptom-free residual trophoblastic tissue 15 months after cesarean section.

Successful implantation occurred after embryo transfer in the presence of an extensive endometrial defect after hysteroscopic resection of residual trophoblastic tissue 15 months after cesarean section. At the end of hysteroscopic surgery the anterior uterine wall seemed smooth, although ultimately no endometrium was left in that part and in parts of the fundus. Thus implantation is possible even with extensive endometrial defects. Interesting facts in this case were, first, the long symptom-free period with residual trophoblastic tissue in the uterus, and, second, successful implantation, pregnancy, and delivery despite at least 30% of endometrial surface being irreversibly destroyed. We suggest hysteroscopic resection as the method of choice for exact and minimally traumatic removal of especially older residual trophoblastic tissue.

Is it possible to recommend an "optimal" postoperative management after hysteroscopic metroplasty? A retrospective study with 52 infertile patients showing a septate uterus.

BACKGROUND: The aim of the retrospective study was to evaluate the "optimal" postoperative management after hysteroscopic metroplasty. METHODS. FIFTY-TWO: infertile patients with a septate uterus were included. Hysteroscopic metroplasty was performed using electrocautery (dissection needle) with postoperative cyclical hormone replacement therapy (HRT) + intrauterine device (IUD) insertion for 3 months (Group 1, n = 22), or HRT alone for 3 months (Group 2, n = 13), or without postoperative therapy (Group 3, n = 17). RESULTS: During a median follow-up of 21+/-16.9 months 40.9% in Group 1, 53.8% in Group 2 and 41.2% in Group 3 (p > 0.05) resulted in ongoing pregnancies. The rates of delivery at term were 53.3%, 64.4% and 88.9%, respectively. CONCLUSIONS: A postoperative 3-months HRT + IUD insertion or a HRT alone after hysteroscopic metroplasty are not necessary.