Effectiveness of the short-term use of Cimicifuga racemosa in the endothelial function of postmenopausal women: a double-blind, randomized, controlled trial.

Objective: This study aimed to assess the effects of daily use of Cimicifuga racemosa on endothelial function through flow-mediated dilation of the brachial artery, when used for 28 days by healthy postmenopausal women.Methods: The double-blind, randomized, placebo-controlled study included two groups of postmenopausal women (n = 31 each). The subjects were clinically assessed and flow-mediated dilation of the brachial artery was measured before and after 28 days of treatment. Patients received dry extract corresponding to 160 mg C. racemosa (extract with 4 mg of triterpene glycosides) or placebo.Results: Mean age, time since menopause, and body mass index in the two groups were similar. The measurements of flow-mediated dilation of the brachial artery, pre and post treatment, respectively, showed a significant increase in patients who used C. racemosa (p = 0.006), unlike patients who used placebo, who did not present changes in the outcome of flow-mediated dilation of the brachial artery after 28 days of use (p ≥ 0.05). When comparing the number of women in both groups who showed an increase in flow-mediated dilation, a significant difference was found in the measurements of the treated group after the use of the medication (p = 0.018).Conclusions: Daily use of 160 mg C. racemosa extract by postmenopausal women for 28 days beneficially influences endothelial function by promoting elasticity of the brachial artery.

Time since menopause, but not age, is associated with increased risk of osteoporosis.

Objectives: This study aimed to determine whether estrogen deficiency is a sole risk factor for osteoporosis or is also associated with age, through indicators such as gender, age, and time since menopause. Methods: A cross-sectional study was conducted evaluating 938 postmenopausal women who underwent bone mineral densitometry. We collected the following data: age, ethnic group, body mass index, smoking, and time since menopause. These data were correlated to the presence of osteoporosis, according to the T-score of the femur and lumbar spine. Results: The prevalence of osteoporosis was 37.8%. Ethnic group (p = 0.47) and smoking habits (p = 0.19) were not associated with osteoporosis. In the group of women with osteoporosis, mean age was significantly higher (p < 0.001), mean body mass index was significantly lower (p < 0.001), and time since menopause was significantly higher (p < 0.001) than in the group of women with no osteoporosis. After multivariate analysis was performed, the only variables that remained independently associated with osteoporosis were body mass index and time since menopause. Higher body mass index was a protective factor (odds ratio = 0.80 [95% confidence interval 0.76; 0.84], p < 0.001). Time since menopause represented a risk factor for osteoporosis (odds ratio = 1.04 [1.02; 1.06], p < 0.001). When divided into categories, the risk increased after 20 years of menopause and gradually every 5 years. Conclusion: Time since menopause and body mass index were the most important factors associated with osteoporosis, confirming that estrogen deficiency, and not age, is the major cause of the disease.

Does freeze-all policy affect IVF outcome in poor ovarian responders?

OBJECTIVE: To evaluate whether the freeze-all strategy affects in-vitro fertilization (IVF) outcome in poor ovarian responders (POR) defined according to the Bologna criteria. METHOD: This was a retrospective cohort study of patients undergoing IVF treatment between January 2012 and December 2016 at a single center. A total of 433 POR (as defined by the Bologna criteria) fulfilled criteria and were included in the study; of these, 277 patients underwent fresh embryo transfer (ET) and 156 followed the freeze-all policy. All patients underwent controlled ovarian stimulation (COS) following a gonadotropin-releasing hormone antagonist protocol, and cleavage-stage ET. Main outcome measure was ongoing pregnancy rate. Secondary outcomes included implantation and clinical pregnancy rates. The freeze-all strategy was implemented when the progesterone serum level was > 1.5 ng/mL or the endometrium was < 7 mm on the trigger day, or as per patient preference. Patients with previous failed fresh ET also underwent fresh ET or freeze-all strategy considering the indications mentioned above. RESULTS: Mean maternal age in the freeze-all group was 39.5 ± 3.6 years and in the fresh ET group was 39.7 ± 3.8 years (P = 0.54). Mean number of embryos transferred (nET) was 1.53 ± 0.6 and 1.60 ± 0.6 (P = 0.12) in the freeze-all and fresh ET groups, respectively. Ongoing pregnancy rate did not differ significantly between the freeze-all and fresh ET groups (9.6% vs 10.1%, respectively; relative risk (RR), 0.95; 95% CI, 0.52-1.73), nor did the clinical pregnancy rate (14.1% vs 13.7%, respectively; RR, 1.03; 95% CI, 0.63-1.67). Implantation rate was 9.6% and 9.8% (P = 0.82) in the freeze-all and fresh ET groups, respectively. Logistic regression analysis (including maternal age, antral follicle count, number of retrieved and mature oocytes, nET, and fresh ET vs freeze-all strategy) indicated that maternal age (P < 0.001) and nET (P = 0.039) were the only independent variables associated with ongoing pregnancy rate. CONCLUSIONS: The freeze-all strategy, compared with fresh ET, had no impact on IVF outcomes in POR patients as defined according to the Bologna criteria. Multicenter studies including large numbers of patients should be carried out to confirm the results of this study and reach conclusions about the potential benefits of the freeze-all policy for poor responders. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Effect of short-term estrogen therapy on endothelial function: a double-blinded, randomized, controlled trial.

OBJECTIVE: To evaluate the effect of short-term hormone replacement therapy with 0.625 mg conjugated estrogens daily on endothelial function of healthy postmenopausal women, using flow-mediated dilation (FMD) of the brachial artery. METHODS: We performed a double-blinded, randomized, controlled trial over 3 years. Randomization was performed using computer-generated sorting. All participants were blinded to the use of conjugated equine estrogens (CEE) or placebo and FMD was assessed by a blinded examiner, before and after 28 days of medication. A total of 64 healthy postmenopausal women were selected and randomly assigned into two groups of treatment: 0.625 mg of CEE or placebo. RESULTS: FMD values were statistically different between the groups (p = 0.025): the group receiving CEE showed a FMD value of 0.011 compared to the placebo group (FMD = -0.082). The two groups were additionally evaluated for homogeneity through the Shapiro-Wilk test in respect to variables that could interfere with endothelial function such as age (p = 0.729), body mass index (p = 0.891), and time since menopause (p = 0.724). Other variables were excluded during selection of the participants such as chronic vascular conditions, smoking, and sedentary lifestyle. CONCLUSION: Our results demonstrate that the administration of 0.625 mg CEE for 28 days is effective in improving vascular nitric oxide-dependent dilation assessed by FMD of the brachial artery in postmenopausal women. CLINICAL TRIAL REGISTRATION: NCT01482416.

Short-term tibolone does not interfere with endothelial function: a double-blinded, randomized, controlled trial.

Objective To evaluate the effect of short-term hormone replacement therapy with tibolone 2.5 mg daily on endothelial function of healthy postmenopausal women, using flow-mediated dilation (FMD) of the brachial artery. Methods We performed a randomized, double-blinded, placebo-controlled study. A total of 100 healthy postmenopausal women were randomly allocated to receive tibolone (n = 50) or placebo (n = 50) for 28 days. Measurement of the FMD of the brachial artery was performed before and after the use of tibolone and placebo. Results A total of 31 women completed the study in the tibolone group, and 32 women completed the study in the control group. The results of the FMD measurements obtained from the women in the two groups before treatment were similar (0.018 and 0.091, for tibolone and placebo, p = 0.57). The values of the FMD in women who used tibolone and placebo, before and after the treatment, were similar in both groups. The numbers of women who presented an increase in the values of the FMD in both groups were also similar. Conclusion Our results demonstrate that the administration of 2.5 mg tibolone to healthy postmenopausal women for 28 days does not promote endothelial-dependent vasodilation, measured by FMD of the brachial artery.

Intracytoplasmic sperm injection outcomes with cryopreserved testicular sperm aspiration samples.

Intracytoplasmic sperm injection (ICSI) may be performed with testicular frozen-thawed spermatozoa in patients with nonobstructive azoospermia (NOA). Sperm retrieval can be performed in advance of oocyte aspiration, as it may avoid the possibility of no recovery of spermatozoa on the day of oocyte pickup. There are few studies available in the literature concerning the use of frozen-thawed spermatozoa obtained from testicular sperm aspiration (TESA). To evaluate the effects and the outcomes of ICSI with frozen-thawed spermatozoa obtained by TESA, we performed a retrospective analysis of 43 ICSI cycles using frozen-thawed TESA. We obtained acceptable results with a fertilisation rate of 67.9%, an implantation rate (IR) of 17.1%, and clinical and ongoing pregnancy rates of 41.9% and 37.2% respectively. The results of this study suggest that performing ICSI using cryopreserved frozen-thawed testicular spermatozoa with TESA as a first option is a viable, safe, economic and effective method for patients with NOA.

Onco-testicular sperm extraction: birth of a healthy baby after fertility preservation in synchronous bilateral testicular cancer and azoospermia.

Testicular germ cell tumours (TGCT) represent 1%-1.5% of all male neoplasms, and they have the highest prevalence among men between 15 and 35 years old. Synchronous bilateral disease is a rare presentation, and the ratio of metachronous to synchronous bilateral disease is about 4 : 1. Several studies have suggested a correlation between male infertility and testicular cancer, with a 20-fold increase in the incidence of testicular cancer in infertile patients compared with the general population. At the time of diagnosis, 50%-75% of patients with unilateral TGCT present with subfertility; almost 13% of the patients are azoospermic before treatment, and up to two-thirds of patients become azoospermic following adjuvant cancer therapies. Therefore, fertility preservation should be considered in all oncological treatments. The only available option to preserve the reproductive potential in azoospermic patients with testicular cancer is to perform an onco-testicular sperm extraction (onco-TESE) before cancer treatment. In this paper, we describe a rare case of a patient with synchronous bilateral testicular cancer and azoospermia who was submitted to onco-TESE, sperm cryopreservation, and which was followed by the delivery of a healthy baby after intracytoplasmic sperm injection (ICSI), emphasising the importance of fertility preservation in oncology patients.

Progesterone increases resistance of ophthalmic and central retinal arteries in climacteric women.

OBJECTIVE: To evaluate the effect of a synthetic progestin on the vascular resistance of the ophthalmic and central retinal arteries in climacteric women, compared to placebo, using transorbital ultrasound with Doppler velocimetry. METHODS: We performed a prospective, randomized, double-blinded, placebo-controlled study with 216 climacteric women. Subjects were randomly allocated to one of two groups: either the group receiving placebo (one pill/day for 30 days) (n = 108) or the group receiving progestin (5 mg medroxyprogesterone acetate/day for 30 days) (n = 108). Transorbital Doppler velocimetric ultrasound was performed, before and after treatment; we measured the pulsatility index, resistance index and systole/diastole ratio. RESULTS: The mean ages of the participants in the study group and the control group were 54 ± 6.2 years (range 48-59 years) and 55 ± 6.8 years (range 46-60 years), respectively. When we compared the effect of the progestin on the central retinal artery before and after treatment, we observed a significant increase after the treatment in all Doppler indices. The same was observed when we compared the effect of the progestin on the ophthalmic artery. In the group of women receiving placebo, the Doppler indices were similar before and after treatment. CONCLUSIONS: Our results demonstrate the existence of a progestogenic vasoconstrictive effect in the ophthalmic and central retinal arteries. As this study provides new data, the observed effect needs further investigations to better elucidate its extent. Moreover, our findings may be particularly useful to others interested in understanding the vascular dynamics of the cerebral vessels and to researchers running clinical trials related to hormone replacement therapy.

Birth of healthy twins after intracytoplasmic sperm injection using ejaculated immotile spermatozoa from a patient with Kartagener's syndrome.

This case report demonstrates a successful pregnancy after ICSI combined with hypo-osmotic swelling test in a couple with Kartagener's syndrome with complete immotile ejaculated spermatozoa. Our result suggests that even for complete immotile spermatozoa, the use of hypo-osmotic swelling test is a good alternative to identify viable spermatozoa. When associated with ICSI, it can be a valuable tool to get fertilisation and pregnancy.

Blastomere development after embryo biopsy: a new model to predict embryo development and to select for transfer.

One of the most important and unsolved problems in in-vitro fertilization is to decide which embryos are more suitable to implant and therefore should be transferred. We analysed the in-vitro development of isolated biopsied blastomeres and compared it to the development of the original embryo, in order to find a relationship that could show the embryo's potential future development and so increase implantation rates. A total of 66 normally fertilized human embryos were biopsied at the 6- to 10-cell stages. At day 6, blastomeres were counted by nuclear labelling. A total of 33 embryos (50%) reached the blastocyst stage. Of the isolated blastomeres, 63% divided and 53% cavitated over 3 days in culture. Of the blastomeres taken from embryos that developed to the blastocyst stage, 88% divided, 79% cavitated, 76% divided and cavitated and 9% neither divided nor cavitated. In those from arrested embryos, 39% divided (P < 0.001), 21% cavitated (P < 0.001), 15% divided and cavitated (P < 0.001) and 55% neither divided nor cavitated (P < 0.001). Blastomeres biopsied from embryos that reached the blastocyst stage showed a significantly higher proportion of division and cavitation than those originated from arrested embryos. Culture of the isolated blastomeres can demonstrate those embryos more likely to develop to the blastocyst stage and that are probably more suitable to implant. Cryopreserving biopsed embryos and culturing blastomeres would increase implantation rates. Embryos can then be selected according to the blastomere development and thawed for transfer in a future cycle.

Doppler colour flow analysis of uterine and ovarian arteries prior to and after surgery for tubal sterilization: a prospective study.

Female sterilization by tubal ligation is a very common method of birth control. A relationship between tubal sterilization and subsequent development of menstrual disorders has been described in the literature but a biological mechanism explaining such an association has not yet been demonstrated. The aim of this study was to evaluate the influence of tubal ligation by the Pomeroy technique on ovarian and uterine artery blood flow using pre- and post-surgical Doppler assessments. We studied prospectively 20 patients undergoing laparotomy for tubal ligation. All patients had a Doppler blood flow assessment before and after surgery, conducted in the mid-follicular phase of their cycle. The pulsatility index (PI) of the right uterine artery ranged from 1.44 to 3.86 (mean 2. 23) when measured prior to surgery and from 1.36 to 2.85 (mean 2.13) when measured after surgery. In the left uterine artery, the PI ranged from 1.67 to 3.17 (mean 2.17) and from 1.69 to 2.88 (mean 2. 22) before and after surgery respectively. The difference was not statistically significant. The PI of the right ovarian artery ranged from 1.38 to 3.48 (mean 2.41) prior to surgery and from 1.48 to 3.23 (mean 2.29) after surgery. In the left ovarian artery, the PI ranged from 1.36 to 3.62 (mean 2.54) and from 1.85 to 4.00 (mean 2.61) before and after surgery respectively. Again, the difference was not statistically significant. Our results suggest that tubal sterilization performed by Pomeroy's technique does not induce immediate alterations in the vascular flow of either ovarian or uterine arteries.

Births after transfer of zona-free blastocysts in oocyte donation cycles.

PURPOSE: Oocyte donation is a well-established method of assisted reproduction for women with irreversible infertility and with previous implantation failures after in vitro fertilization. Although the pregnancy rates are very high, sometimes implantation does not occur even after various attempts. We report the first two cases of transfer of zona-free blastocysts in oocyte donation cycles that developed to normal pregnancies and births. METHODS: The patients had undergone three previous standard oocyte donation cycles with failure of implantation. Endometrium preparation was performed after suppression of the pituitary function, with E2 valerate and Progesterone at the day of oocyte retrieval. Normally fertilized embryos were cultured in Earle's culture medium until Day 3 and in S2 medium until Day 5. For each patient, the zonae of two fully expanded blastocysts were enzymatically removed with 0.5% pronase. Zona-free blastocysts were transferred for the patients 2 h later. RESULTS: On Day 12 after transfer, pregnancies were confirmed with elevated serum levels of beta hCG. A gestational sac with a foetal heart beat was seen by ultrasound 15 days later, in each patient. Normal healthy babies were born at 38 and 39 weeks of pregnancy. CONCLUSIONS: This is the first report of successful pregnancies and births after oocyte donation and transfer of zona-free blastocysts in human. It not only shows the feasibility of the treatment but also opens a new alternative for the patients with repetitive implantation failure after OD cycles.

Proliferation of blastomeres from biopsied cleavage stage human embryos in vitro: an alternative to blastocyst biopsy for preimplantation diagnosis.

Normally fertilized human embryos were biopsied at cleavage stages on the third day after in-vitro fertilization (IVF). One or two blastomeres at the 8-cell stage were removed and co-cultured with the biopsied embryos. Embryos and blastomeres were assessed daily for morphological development until day 6, when the number of cells were counted by labelling the nuclei. In all, 53% of the biopsied embryos (25 out of 47) reached the blastocyst stage between day 5 and 6 and the proportion was the same irrespective of the number of cells removed. There was no significant difference between biopsied embryos from which one or two blastomeres respectively had been removed with regard to total cell numbers at the blastocyst stage (56.2 +/- 3.0 and 64.7 +/- 5.5), number of trophectoderm (45.4 +/- 3.5 and 44.0 +/- 5.7) and inner cell mass cells (14.0 +/- 1.2 and 16.6 +/- 1.8). Overall, 72% of the isolated blastomers divided at least once over 3 days in culture and 50% divided more than once. The mean overall cell number after 3 days in culture was 3.7 +/- 0.48 per blastomere (range 1-8 cells) if one cell was removed and 6.9 +/- 1.0 if two cells were removed. If the undivided blastomeres are excluded, the mean cell number was 4.8 +/- 0.51 and 8.3 +/- 1.0 respectively. Over this period, 55% of the blastomeres cavitated. Of the blastomeres taken from embryos that developed to the blastocyst stage, 92% divided and 76% cavitated. In those from arrested embryos, 50% divided (P < 0.002) and 32% cavitated (P < 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Results of IVF in patients with endometriosis: the severity of the disease does not affect outcome, or the incidence of miscarriage.

The literature suggests that the results of in-vitro fertilization (IVF) for patients with endometriosis depend on the stage of the disease, and that patients with severe endometriosis have a higher failure rate. Miscarriage is said to be more prevalent in women treated for endometriosis. In the study reported here, 140 patients with endometriosis underwent 182 cycles of IVF using gonadotrophin-releasing hormone analogues (GnRHa). Patients with endometriosis only were allocated to one group (group 4). The results were compared with those of three other groups of patients undergoing the same treatment within the same period. Group 1 consisted of couples with male factor only (45 cycles), group 2, couples with unexplained infertility (196 cycles) and group 3, couples with a tubal factor only (1139 cycles). The mean age of the patients, mean number of human menopausal gonadotrophin (HMG) ampoules administered, oestradiol concentration on the day of human chorionic gonadotrophin administration, number of days of HMG, mean number of oocytes retrieved and retrieval rate were not significantly different. The fertilization rate was significantly lower in group 1; no difference was observed in the other three groups. The mean number of normally fertilized embryos was not significantly different. The number of transferred embryos in each cycle and the implantation rates were similar in the four groups. The overall pregnancy rate per transfer was 39% in group 1, 48% in group 2, 45% in group 3 and 40% in group 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical experience with preimplantation diagnosis of sex by dual fluorescent in situ hybridization.

PURPOSE: Our purpose was to assess the clinical application of dual fluorescent in situ hybridization (FISH) for the diagnosis of sex in the human preimplantation embryo. RESULTS: Over a 2-year period, 18 couples at risk of transmitting X-linked recessive disorders underwent preimplantation diagnosis of embryo sex by dual FISH with X and Y chromosome-specific DNA probes. A total of 27 in vitro fertilization (IVF) treatment cycles led to nine pregnancies; 7 reached the stage of clinical recognition, of which 2 spontaneously aborted. There were five live births, three singleton and two twin: none in disagreement with the diagnosed sex. The diagnosis was corroborated in 51 of the 74 nontransferred embryos. The efficiency of the procedure improved throughout the four treatment cycles. This was reflected in the increased proportion of double embryo transfers (from 50% in series 1 and 2 to 100% in series 3 and 4), with a consequent improvement in pregnancy rate (from 28 to 71% per embryo transfer). The excess of male embryos (male:female, 60:40 overall) and the high proportion of biopsied embryos with abnormal numbers of X and Y chromosome signals (14.5%) effectively reduced the number of normal female embryos available for transfer. CONCLUSION: Dual FISH is an efficient technique for determination of the sex of human preimplantation embryos and the additional ability to detect abnormal chromosome copy numbers, which is not possible via the polymerase chain reaction, (PCR), makes FISH the preferred technique.